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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 19 recordsLinked to original sources

Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion imaging with positron emission tomography.

A rubidium-82 ((82)Rb) elution system is described for use with positron emission tomography. Due to the short half-life of (82)Rb (76 s), the system physics must be modelled precisely to account for transport delay and the associated activity decay and dispersion. Saline flow is switched between a (82)Sr/(82)Rb generator and a bypass line to achieve a constant-activity elution of (82)Rb. Pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control (PCC) algorithm is developed which produces a constant-activity elution within the constraints of long feedback delay and short elution time. The system model parameters are adjusted through a self-tuning algorithm to minimize error versus the requested time-activity profile. The system is self-calibrating with 2.5% repeatability, independent of generator activity and elution flow rate. Accurate 30 s constant-activity elutions of 10-70% of the total generator activity are achieved using both control methods. The combined PWM-PCC method provides significant improvement in precision and accuracy of the requested elution profiles. The (82)Rb elution system produces accurate and reproducible constant-activity elution profiles of (82)Rb activity, independent of parent (82)Sr activity in the generator. More reproducible elution profiles may improve the quality of clinical and research PET perfusion studies using (82)Rb.

Algorithms↗

Diagnostic relevance of the determination of lymphocyte subpopulations in environmental medicine.

Earlier hopes that determination of lymphocyte subpopulations might become a strong diagnostic tool in environmental medicine have not been fulfilled in recent years. Analysis of the scientific literature rather shows that there are only few examples for environmental exposures causing reproducible shifts of lymphocyte subpopulations. Moreover, current knowledge suggests that "environmental diseases" are not associated with characteristic changes of subpopulation patterns. If lymphocyte subpopulations are analyzed, each diagnostic step, including indication, sample handling, analytic procedure and data-interpretation, should adhere to good quality criteria. Taking all together, the determination of lymphocyte subpopulations in the context of environmental medicine comes under category IV of the criteria of the Commission for Methods and Quality Assurance in Environmental Medicine of the German federal health authority (Robert Koch-Institute; RKI): "A procedure cannot be recommended because there is not sufficient information to justify it" (here: no solid trends in epidemiological examinations), "and because theoretical considerations speak against an application" (here: high physiological variability and missing exposure or substance specificity).

Antigens, CD↗

The lysogenic region of virus phiCh1: identification of a repressor-operator system and determination of its activity in halophilic Archaea.

phiCh1 is a temperate virus infecting the haloalkaliphilic archaeon Natrialba magadii. As for all temperate viruses, a control of the lysogenic state versus the lytic life cycle is essential. Two open reading frames (ORFs) have been identified as putative repressor encoding genes: ORF48 and ORF49. The protein of ORF48 showed sequence similarities to putative repressor molecules. ORF49 was identified by the analysis of a mutant of phiCh1: the lysogenic strain carrying mutant phiCh1-1 showed a different lysis behavior than wild type virus phiCh1, indicating a dysfunction in the regulation of gene expression. Here, we show that the intergenic region between ORF48 and ORF49 comprises a promoter/operator sequence that is a transcriptionally active region in the model system Haloferax volcanii. Transcription from this region can be repressed by the activity of the ORF48 gene product. Gp43/gp44 has an enhancing effect on this regulatory sequence. Evidence is given for a possible binding site of Rep and gp43/gp44 within the coding region of the rep gene.

Archaeal Viruses↗

Physical activity and the 15-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study.

BACKGROUND: Cardiovascular disease and age-related macular degeneration (AMD) may share common risk factors. Physical activity improves the cardiovascular risk profile; however, there have been few studies investigating a relationship between physical activity and the long-term incidence of AMD. METHODS: The 15-year cumulative incidence of AMD was determined through four examination phases at 5-year intervals of a population-based study conducted in Beaver Dam, Wisconsin, USA, initiated in 1988-90 (n = 3874 men and women between ages 43 and 86 years). Early AMD (pigment abnormalities or soft indistinct drusen), exudative AMD and geographic atrophy were determined by grading stereoscopic colour fundus photographs. Measures of physical activity were obtained through a questionnaire administered at the baseline examination. RESULTS: After controlling for age, sex, history of arthritis, systolic blood pressure, body mass index, smoking and education, people with an active lifestyle (defined as regular activity > or =3 times/week) at baseline were less likely to develop exudative AMD (odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1 to 0.7) compared with people without an active lifestyle. After multivariate adjustment, increased categories of number of blocks walked per day decreased the risk of exudative AMD (OR 0.7, 95% CI 0.6 to 0.97). Physical activity was not related to the incidence of early AMD or pure geographic atrophy. CONCLUSIONS: These data show a protective effect of physical activity for incident exudative AMD, independent of body mass index and other confounders. They also suggest a possible modifiable behaviour that might be protective against developing AMD.

Adult↗

The association between serum uric acid level and long-term incidence of hypertension: Population-based cohort study.

Increasing experimental evidence, including recently developed animal models support a causal role for uric acid in the development of hypertension. However, it is not clear whether serum uric acid levels are independently associated with the long-term incidence of hypertension. We examined the association between serum uric acid levels and 10-year incidence of hypertension in a population-based cohort study based in Beaver Dam city and township, Wisconsin, US. We studied 2520 hypertension-free individuals (56.3% women, age: 43-84 years, 98% Caucasian) at the baseline examination (1988-1990). The main outcome of interest was hypertension (systolic blood pressure (BP) of 140 mm Hg or higher, diastolic BP 90 mm Hg or higher, or combination of self-reported high BP diagnosis and use of antihypertensive medications) incidence over 10 years among baseline normotensive individuals. Nine hundred and fifty-six individuals developed hypertension over a 10-year follow-up period. The relative risk (RR) (95% confidence intervals (CI)) of incident hypertension increased in a dose-dependent manner (P-trend < 0.05 in all models) with increasing uric acid quartiles. Multivariable RR (95% CI) comparing the highest quartile of serum uric acid (> or =390 micromol/l) to the lowest quartile (< or =260 micromol/l) was 1.65 (1.41-1.93). This association persisted in subgroup analyses by categories of smoking, alcohol intake, body mass index, baseline blood pressure and estimated glomerular filtration rate (GFR). In conclusion, increasing quartiles of serum uric acid was associated with 10-year incidence of hypertension independent of smoking, alcohol intake and baseline kidney function suggesting an independent positive association between serum uric acid levels and hypertension development among community-dwelling older adults.

Adult↗

Retinal vascular calibre and the risk of coronary heart disease-related death.

OBJECTIVE: To examine whether retinal vascular calibre independently predicts risk of coronary heart disease (CHD) -related death. METHODS: In a population-based cohort study of 3654 Australians aged > or = 49 years, retinal arteriolar and venular calibres were measured from baseline retinal photographs and the arteriole to venule ratio (AVR) was calculated. CHD-related death was confirmed from the Australian National Death Index. RESULTS: Over nine years, 78 women (4.1%) and 114 men (7.8%) had incident CHD-related deaths. In people aged 49-75 years, wider venules were associated with CHD death, with relative risk (RR) 1.8 (95% confidence interval (CI) 1.1 to 2.7) and RR 2.0 (95% CI 1.1 to 3.6) per standard deviation (SD) increase in venular calibre for men and women, respectively, after adjustment for traditional risk factors. Additionally, in women aged 49-75 years, smaller AVR and narrower arterioles were associated with CHD death (RR 1.5, 95% CI 1.1 to 2.2, and RR 1.9, 95% CI 1.0 to 3.5 per SD decrease in AVR and arteriolar calibre, respectively, after adjustment). These associations were not observed in people aged > 75 years. CONCLUSIONS: These findings suggest that microvascular disease processes may have a role in CHD development in middle-aged people, particularly in women. Retinal photography may be useful in cardiovascular risk prediction.

Aged↗

Activity standardization and nuclear decay data of 109Cd.

The activity of a (109)Cd solution has been accurately determined without using (109)Cd nuclear decay data such as emission probabilities. An ampoule containing this calibrated (109)Cd solution was sent to the Bureau International des Poids et Mesures to include the activity result in the database of the International Reference System (SIR). The emission rate of conversion electrons was measured by means of pressurized proportional counters as well as by a liquid scintillation spectrometer. The combination of the results with the photon emission rate measured with the aid of gamma-ray spectrometers yields the activity concentration. The measurement results were also used to deduce emission probabilities with high accuracy. For the 88 keV transition, a photon emission probability of p(gamma)=0.03663(33) and a total internal conversion coefficient of alpha(t)=26.30(25) were determined.

Journal Article↗

A modified method for the characterisation and activity determination of large area sources.

Large area sources emitting alpha and beta radiations, respectively, are often used for calibrations of surface contamination monitors and meters. It is well known, however, that their properties are strongly influenced by their construction and by their active layer preparation. Non-uniformity of activity distributions over the active surface and the thickness of absorption and backscattering layers cause changes not only in the ratio of particle emission rate and activity but also in emitted particle spectra distributions. Consequently, different sources need to be characterised by one or more parameters related to their emitted particle spectra and used for their activity determination. A modified method based on simple particle absorption spectrometry has been developed. The correlation between a source characteristic parameter and its radiation detection efficiency is utilised for its activity estimation.

Calibration↗

Standardization and nuclear decay data of 65Zn.

Standardization by means of 4pibeta-gamma coincidence counting was applied to calibrate a 65Zn solution within the scope of EUROMET project no. 721. The activity result was combined with gamma-ray spectrometry measurements to investigate the photon emission probabilities. The half-life of 65Zn was measured with improved accuracy by means of 4pi ionization chamber measuring systems that were also used for secondary activity determination. In addition, we tested a new secondary standardization procedure by means of liquid scintillation counting.

Algorithms↗

[Pain management and coping behaviour in premature babies (< 1500 g) at corrected age of 36 months influence of neonatal experience and maternal anxiety].

INTRODUCTION: Neonatal experience of pain and distress can lead to developmental problems, which can be associated with long-term emotional and behavioural disorders. The aim of the study was to analyse the effects of early experiences of pain and maternal reactions on the pain and coping behaviour of preterm infants. METHODS: In a prospective longitudinal study of 69 very low birth weight (VLBW) preterm infants, neonatal data regarding painful manipulations, analgesics and sedatives, and general medical condition (Nursery Neurobiological Risk Score; NBRS) were assessed. At the (corrected) age of 36 months, 53 preterm infants and a control group of 23 full-term infants were re-examined. Pain and coping behaviour were estimated by a questionnaire. Maternal anxiety was assessed in semi-structured interviews at the age of 3, 12 and 36 months in the preterm group. RESULTS: The mean gestational age was 29 + 0 weeks (23 + 3 to 34 + 1), the mean birth weight 1058 g (380 to 1480 g) in preterms and 39 + 3 weeks (37 + 0 to 42 + 0) and 3379 g (2400 to 4130 g), respectively, for the full-terms. The sex ratio was equal, 45.3 % of the preterms were multiples (controls 34.8 %). Preterms had higher descriptive scores for all types of pain situations. After controlling for other associated factors, a negative correlation between birth weight and later pain behaviour in medical situations remained. Preterms had a more negative coping behaviour during every day injuries. In terms of coping behaviour, only a shorter inpatient treatment in the neonatal period was associated with social withdrawal after controlling for other associated factors. Maternal anxiety at the age of 12 and 36 months was associated with negative coping behaviour following simple injuries. CONCLUSIONS: While preterms do not have a higher pain threshold in general, a subgroup does have a higher risk for later sensation to pain. Preterms use more unfavourable coping strategies in simple injuries which, in turn, seem to be decisively mediated by maternal anxiety. Future research should focus on psycho-social factors involved in the development of pain reactions, as these can predispose towards behavioural disorders.

Adaptation, Psychological↗

Do retinopathy signs in non-diabetic individuals predict the subsequent risk of diabetes?

BACKGROUND/AIMS: Isolated retinopathy signs are common in non-diabetic individuals and have been shown to be associated with impaired glucose metabolism. In a cohort of people without diabetes, the association of these retinopathy signs and subsequent development of diabetes were examined. METHODS: A population based cohort study of 7992 people aged 49-73 years without diabetes was conducted. Retinal photographs of these participants were evaluated for the presence of retinopathy signs according to a standardised protocol. Incident cases of diabetes were identified prospectively. RESULTS: After a follow up of 3 years, 291 (3.6%) people developed incident diabetes. In the total cohort, retinopathy was not significantly associated with incident diabetes (4.7% v 3.6%, multivariable adjusted odds ratio (OR) 1.1, 95% confidence intervals (CI), 0.7 to 1.9). However, among participants with a positive family history of diabetes, retinopathy was associated with incident diabetes (10.4% v 4.8%, multivariable adjusted OR 2.3, 95% CI, 1.0 to 5.3). Among participants without a family history of diabetes, retinopathy was not associated with incident diabetes CONCLUSIONS: In individuals with a family history of diabetes, retinopathy signs predict subsequent risk of clinical diabetes.

Aged↗

Short amplicon STR multiplex for stain typing.

We developed a short tandem repeat (STR) typing kit based on DNA database systems that are included in, for example, the Interpol Standard Set of Loci recommendations (i.e., TH01, VWA, D3S1358, FGA) and the gender typing system Amelogenin. Two different multiplex sets were tested using the fluorescent dyes FAM, JOE, and VIC. The PCR results were compared to the commercially available AmpFISTR Blue kit, which contains the STRs D3S1358, VWA, and FGA. The advantage of our multiplex compared with the Blue kit was the generation of shorter amplicons (<200 bp) and the higher combined power of discrimination.

Amelogenin↗

Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects.

OBJECTIVE: Various immunological effects have been reported during application of mistletoe preparations. Because these data are heterogeneous, we performed a placebo controlled study to investigate (1) effects on peripheral granulocyte and eosinophil counts, (2) related cytokine levels and (3) whether effects are related to mistletoe lectin (ML). METHODS: 43 volunteers were randomized to receive the mistletoe plant extract Iscador Quercus spezial (IQ), purified ML, IQ which was depleted from ML, or placebo subcutaneously twice per week for 8 weeks. Weekly, differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells (PBMC) were analyzed. RESULTS: Leukocyte-, granulocyte-, and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group. Furthermore, a significant increase of antigen-induced production of GM-CSF, IL-5 and IFNgamma by PBMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo. Severe side effects did not occur in any of the subjects. CONCLUSIONS: Treatment with IQ or ML stimulates the production of GM-CSF, IL-5 and IFNgamma by PBMC, and this is accompanied by an increase of eosinophil- and granulocyte-counts. These observations may, therefore, open rational therapeutic indications for mistletoe extracts.

Adult↗

Retinal microvascular signs and risk of stroke and stroke mortality.

OBJECTIVE: The purpose of this study was to assess the relation of retinal microvascular signs and incident stroke and stroke mortality in an older population. METHODS: The authors took retinal photographs on baseline participants (3,654 patients aged 49+ years) of the Blue Mountains Eye Study (1992 to 1994). They assessed the presence of retinopathy (microaneurysms, retinal hemorrhages) in participants without diabetes and retinal arteriolar signs in all participants using standardized grading protocols. Incident stroke/TIA/cerebrovascular death (combined stroke events) were identified at follow-up examinations during 1997 to 1999. RESULTS: During a 7-year period, 859 participants died, 97 (11.3%) of which died of cerebrovascular causes. Of survivors, 24 had confirmed incident stroke, and 11 had incident TIA. Combined stroke events were more frequent in participants with retinopathy (5.7%), with moderate/severe arteriovenous nicking (4.2%), or with focal arteriolar narrowing (7.2%) compared with those without (1.9%). After controlling for age, sex, systolic blood pressure, smoking, and self-rated health, retinopathy was significantly associated with combined stroke events (relative risk [RR] 1.7, 95% CI 1.0 to 2.8) in persons without diabetes. This association was stronger in those without severe hypertension (RR 2.7, CI 1.2 to 6.2) or in persons with two or more retinal microvascular signs (RR 2.7, CI 1.5 to 5.2). Generalized or focal arteriolar narrowing or arteriovenous nicking was not independently associated with combined stroke events after multivariate adjustment. CONCLUSIONS: In older Australians without diabetes, retinopathy signs predict stroke or stroke-related death independent of traditional stroke risk factors.

Age Factors↗

In vitro study on the immunological effect of bromelain and trypsin on mononuclear cells from humans.

BACKGROUND: Proteolytic enzymes such as bromelain and trypsin are used as an adjuvant therapeutic approach in the treatment of chronic inflammatory, malignant and autoimmune diseases. In vitro studies have shown that proteolytic enzymes modulate surface adhesion molecules on T-cells. In this study we analysed the influence of bromelain and trypsin on the cytokine production and proliferation of peripheral blood mononuclear cells (PBMC) from patients with a classical cellular mediated autoimmune disorder, namely encephalomyelitis disseminata (ED) as well as from healthy controls. - METHODS: PBMC from patients with ED (n=12) and healthy controls (n=12) were cultured for seven days at 37 degrees C under three different conditions: without antigen, with bromelain and with trypsin (final concentrations 10-1000 microg/ml). Proliferation was determined by superset3H-thymidine incorporation. Secretion of cytokines into the supernatant was measured by a double sandwich ELISA. Intracellular cytokines were determined by flow cytometric analysis. - RESULTS: PBMC from patients with ED and healthy controls showed a significantly increased proliferative response to bromelain (ED: 14053+/- 7585 cpm with bromelain vs. spontaneous proliferation of 430+/- 255 cpm; healthy controls: 10689+/- 4607 cpm vs. 327+/-193) but not to trypsin. Bromelain induced in all 24 individuals a significant increase of the macro-phage/monocyte associated cytokines interleukin (IL)-6, granulocyte-macrophage-colony stimulating factor (GM-CSF), tumour necrosis factor alpha (TNFa) (p<0.01) as well as of the type 1 cytokine gamma-interferon (IFNgamma). In contrast, the type 2 cytokines IL-4 and IL-5 were not induced. Flow cytometric analysis revealed a significant increase of IFNgamma-producing CD4+ T-cells. There were no differences in cytokine production between ED patients and healthy controls. - CONCLUSION: These results indicate that bromelain - but not trypsin - activates macrophages/monocytes and type 1 cells independently from the underlying disease and may stimulate, therefore, the innate as well as the adaptive immune system.

Adult↗

Dyslipidaemia and microvascular disease in the retina.

PURPOSE: There are few data on the effect of serum lipids on microvascular disease. This study assessed the relationships between serum lipid levels and microvascular disease, as seen in the retina, among participants who attended a population-based study in Australia (n=3654, aged 49+years). METHODS: Diameters of retinal arterioles and venules were measured from digitised photographs of each participant to obtain an estimate of generalised arteriolar narrowing. Focal arteriolar narrowing, arteriovenous nicking, and retinopathy lesions (microaneurysms, haemorrhages, hard/soft exudates) were graded using a standard protocol. Fasting blood tests were performed in 89% of subjects. Adjusted means were calculated using general linear models. Logistic regression models were used to determine the odds ratios for retinal microvascular signs. RESULTS: After controlling for age, sex, body mass index, smoking, and mean arterial blood pressure, elevated high-density lipoprotein cholesterol was associated with narrower retinal arterioles (Ptrend=0.002) and venules (Ptrend=0.03) and with increased odds of generalised arteriolar narrowing (odds ratio 1.6, 95% confidence interval 1.1-2.2 for the highest vs the lowest quintile of high-density lipoprotein cholesterol). Serum triglyceride had a U-shaped relationship with venular diameter (Ptrend=0.003). We found no consistent pattern of association between serum total cholesterol or low-density lipoprotein cholesterol and any retinal microvascular signs. CONCLUSIONS: These findings suggest that microvascular disease in the retina may result from processes distinct from dyslipidaemia.

Aged↗

3D reconstruction of dental specimens from 2D histological images and microCT-scans.

Direct comparison of experimental and theoretical results in biomechanical studies requires a careful reconstruction of specimen surfaces to achieve a satisfactory congruence for validation. In this paper a semi-automatic approach is described to reconstruct triangular boundary representations from images originating from, either histological sections or microCT-, CT- or MRI-data, respectively. In a user-guided first step, planar 2D contours were extracted for every material of interest, using image segmentation techniques. In a second step, standard 2D triangulation algorithms were used to derive high quality mesh representations of the underlying surfaces. This was accomplished by converting the 2D meshes into 3D meshes by a novel lifting procedure. The meshes can be imported as is into finite element programme packages such as Marc/Mentat or COSMOS/M. Accuracy and feasibility of the algorithm is demonstrated by reconstructing several specimens as examples and comparing simulated results with available measurements performed on the original objects.

Algorithms↗

Intraocular pressure and systemic blood pressure: longitudinal perspective: the Beaver Dam Eye Study.

AIM: To investigate the relation between change in systemic blood pressures and change in intraocular pressure. METHODS: This was a population based study of people 43-86 years old living in Beaver Dam, Wisconsin. Measurements at baseline (1988-90) and 5 year follow up of systemic blood pressures, intraocular pressures, and history of use of blood pressure medications. RESULTS: Intraocular pressures were significantly correlated with systolic and diastolic blood pressures at both baseline and follow up. There were significant direct correlations between changes in systemic blood pressures and changes in intraocular pressure. There was a 0.21 (95% CI: 0.16 to 0.27) mm Hg increase in IOP for a 10 mm Hg increase in systolic and 0.43 (0.35 to 0.52) mm Hg increase in IOP for a 10 mm Hg increase in diastolic blood pressure. Further adjustment for diabetes and medication use did not alter these associations. Decreased systolic or diastolic blood pressures of more than 10 mm Hg over 5 years were significantly associated with decreased IOP. CONCLUSIONS: Reduced systemic blood pressure is associated with reduced intraocular pressure. This finding should be evaluated in other studies, especially with respect to the possibility of resultant decreased risk of open angle glaucoma.

Adult↗