[Recommendations for the expert witness on expert testimony].
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Biomedical subjects
Publications and source records attributed to V Kaiser.
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Innate immunity provides an ever-present or rapidly inducible initial defense against microbial infection. Among the effector molecules of this defense in many species are broad-spectrum antimicrobial peptides. Tracheal antimicrobial peptide (TAP) was the first discovered member of the beta-defensin family of mammalian antimicrobial peptides. TAP is expressed in the ciliated epithelium of the bovine trachea, and its mRNA levels are dramatically increased upon stimulation with bacteria or bacterial lipopolysaccharide (LPS). We report here that this induction by LPS is regulated at the level of transcription. Furthermore, the transfection of reporter gene constructs into tracheal epithelial cells indicates that DNA sequences in the 5' flanking region of the TAP gene, within 324 nucleotides of the transcription start site, are responsible in part for mediating gene induction. This region includes consensus binding sites for NF-kappaB and nuclear factor interleukin-6 (NF IL-6) transcription factors. Gel mobility shift assays indicate that LPS induces NF-kappaB binding activity in the nuclei of these cells, while NF IL-6 binding activity is constitutively present. The gene encoding human beta-defensin 2, a human homologue of TAP with similar inducible expression patterns in the airway, was cloned and found to have conserved NF-kappaB and NF IL-6 consensus binding sites in its 5' flanking region. Previous studies of antimicrobial peptides from insects indicated that their induction by infectious microbes and microbial products also occurs via activation of NF-kappaB-like and NF IL-6-like transcription factors. Together, these observations indicate that a strategy for the induction of peptide-based antimicrobial innate immunity is conserved among evolutionarily diverse organisms.
Antimicrobial peptides are a prevalent mechanism of host defense found throughout nature. In mammals, defensins are among the most abundant of these broad-spectrum antibiotics, and are expressed in epithelial and hematopoietic cells. The defensin peptides are especially abundant in neutrophils; however, gene expression is limited to the promyelocyte stage. In epithelial cells, defensin genes are found as both constitutively expressed and inducible. Induction has been observed in vitro by stimulation with bacterial lipopolysaccharide as well as inflammatory mediators. In vivo, up-regulation of several defensin genes occurs in both infectious and inflammatory states. Gene regulation occurs via signal transduction pathways common to other innate immune responses, utilizing transcription factors such as nuclear factor (NF)-kappaB and NF interleukin-6. Together, the data suggest a broad-based innate host defense whereby potent antimicrobial peptides are present to prevent initial colonization by pathogenic microorganisms. In addition, the recognition of bacteria coupled with a nascent inflammatory response can bolster this defense by a coordinated up-regulation of the peptides.
OBJECTIVES: to estimate the intra-observer variability of the measurement of the ankle-brachial systolic pressure index (ABPI) and to compare the reproducibility of the measurements by experienced vascular laboratory assistants and by less-experienced general practice personnel. DESIGN: repeated measurement of ABPI by general practitioners (GPs), GP-assistants and vascular laboratory assistants using a pocket Doppler device and a random-zero sphygmomanometer. METHODS AND MATERIALS: ABPI was measured in six patients with various degrees of PAOD by two experienced observers (vascular laboratory assistants) and by 24 less-experienced observers (18 practice assistants, six GPs). RESULTS: the total number of measurements was 354. The overall intra-observer variability estimate was 11.8% ABPI. The intra-observer variability was 7.3% in the experienced observers and 12.0% in the less-experienced observers. The difference of variability between experienced and less-experienced observers was significant. CONCLUSIONS: the ABPI is suitable in follow-up studies where repeated measurements are needed. Differences between measurements can be minimised by performing repeated measurements or by using more experienced observers.
OBJECTIVES: To describe the risk-factor profile and cardiovascular comorbidity of asymptomatic peripheral arterial occlusive disease (PAOD). DESIGN: A cross-sectional survey. Asymptomatic PAOD was defined as an ankle-brachial pressure index < 0.95, measured on two consecutive occasions, without intermittent claudication. Logistic regression analyses were performed to investigate independent associations between age, gender, smoking status, hypertension, obesity, diabetes, hypercholesterolaemia, physical activity, a family history of cardiovascular disease, the occurrence of ischaemic heart disease and cerebrovascular disease (CeVD) and asymptomatic PAOD. SETTING: 18 general practices in the province of Limburg, the Netherlands. SUBJECTS: A total of 3650 subjects, aged 40-78 years. MAIN RESULTS: Asymptomatic PAOD was present in 8.6% (n = 314) and symptomatic disease in 3.8% (n = 138) of the participants. Age, smoking status, hypertension, and diabetes were significantly associated with asymptomatic PAOD. The ratio of asymptomatic to symptomatic PAOD was higher among the younger age groups. Male gender, hypertension and smoking status were stronger associated with symptomatic PAOD compared with asymptomatic PAOD. Asymptomatic subjects had more IHD and CeVD comorbidity compared with the healthy population. CONCLUSION: Our findings suggest that the risk-factor profile and cardiovascular comorbidity of asymptomatic subjects is comparable to claudicants. Preventive efforts could be made to diminish the influence of especially smoking, diabetes and hypertension in asymptomatic subjects.
We investigated the value of the ankle-brachial systolic pressure index (ABPI) as a test for the diagnosis of peripheral arterial occlusive disease (PAOD) in general practice. ABPI measurements on 231 legs of 117 subjects performed in three general practice centers (GPC) were compared with the diagnostic conclusions of a Vascular Laboratory. The optimum cutoff value for the ABPI, its accuracy and diagnostic value were estimated. In a subpopulation of 51 subjects for whom repeated measurements were available, we checked whether taking the mean of three consecutive ABPIs for test outcome would enhance diagnostic performance. Receiver Operating Characteristic analysis showed that overall performance of the GPC ABPI was good (area under the curve approximately 0.9). Performing repeated ABPI measurements was superior to performing a single measurement. The optimum cutoff value for the ABPI was 0.97, associated with a diagnostic odds ratio (OR) of 17 and an accuracy of 81%. In a somewhat more selected subpopulation, the optimum cutoff value was 0.92 (OR 70, accuracy 90%). On the basis of our results, we suggest the following rule of thumb: if the ABPI < 0.8 or if the mean of three ABPIs < 0.9, it is highly probable that PAOD is present (PV+ > or = 95%); if the ABPI > 1.1 or if the mean of three ABPIs > 1.0, PAOD can be ruled out (PV- > or = 99%). In conclusion, in primary health care, the ABPI measurement can be a useful supplementary test in ambiguous diagnostic situations with regard to PAOD.
BACKGROUND: The prevalence of peripheral arterial occlusive disease (PAOD), including asymptomatic cases and cases unknown to the general practitioner (GP) was estimated in 18,884 men and women, aged 45-74 years, on the list of 18 general practice centres (GPC). METHODS: The study population (n = 3171) consisted of a stratified sample of the total population. In the GPC data were collected on intermittent claudication (IC), peripheral pulses, vascular risk factors, cardio- and cerebrovascular disease (CCVD) and the ankle brachial systolic pressure ratio (AB ratio) and PAOD was defined as an AB ratio < 0.95 on two consecutive occasions. Results were recalculated for the total population. RESULTS: The prevalence of PAOD was 6.9 percent (95 percent Cl:5.2-7.9 percent), a quarter of which (1.6 percent) met the classic WHO criteria. Peripheral arterial occlusive disease did not occur significantly more often among men than among women but men suffered more often from an advanced stage of PAOD. Of all PAOD cases, 22 percent were symptomatic. The proportion of symptomatic cases correlated positively with higher age, male gender and lower AB ratio. Among asymptomatic PAOD cases the prevelance of concomitant CCVD was three to four times as high as in the group of subjects without PAOD. Of all PAOD cases 68 percent were unknown to the GP and this group mainly represented less advanced cases of atherosclerosis. However, among PAOD cases with an AB ratio <0.75, 42 percent were unknown to the GP. CONCLUSIONS: Our data on asymptomatic and unknown PAOD cases show that GPs can still enhance their efforts towards (secondary) prevention of atherosclerosis.
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Over and above the medical problems, AIDS also presents manifold and likewise still mostly undecided or at least not yet uniformly rated aspects. This article is a roughly sketched attempt at reviewing a few essential complexes at the interface between accident surgery and statutory accident insurance. Special attention is drawn to the update addendum.
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One of the non-invasive techniques used in the diagnosis of patients with peripheral arterial occlusive disease is the measurement of the Ankle-Arm Systolic Pressure Ratio ("AA-Ratio"). The magnitude of different sources of measurement variation, relevant to clinical practice as well as multi-observer studies, was estimated from a random effects analysis of variance model. Thirty-five GPs and 24 practice assistants performed 503 AA-Ratio measurements on nine patients over a period of nine weeks, using pocket Doppler devices. When the AA-Ratio is used for diagnostic purposes, a 95% prediction interval consisting of the measured value +/- 15-20% AA-Ratio has to be taken into account. Furthermore, when the AA-Ratio is used in the follow-up of a patient with vascular disease, the difference between two subsequent measurements has to be at least 15.6-19.0% AA-Ratio to have an 80% certainty that this difference is not due to (intra-observer) measurement error.