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S Faber

Publications and source records attributed to S Faber.

34 records · Page 2Linked to original sources

[Sex-specific analysis of cartilage volume in the knee joint--a quantitative MRI-based study].

The objective of the present study was to determine differences in the normal knee joint cartilage volume of males and females, the analysis of the percentage distribution of the cartilage tissue onto the various joint surfaces, and the determination of the relationship between the cartilage volume, the body weight, and the tibial head diameter. We examined the knee joints of nine healthy men and nine women with a low level of physical activity. The cartilage volume was assessed with magnetic resonance imaging, applying a fat-suppressed gradient-echo sequence with a resolution of 2 x 0.31 x 0.31 mm3 and 3D image reconstruction. In the men, the absolute volumes of the femur and tibia, but not those of the patella, were significantly higher than in the women. The differences between the sexes were considerably lower after normalisation to the body weight and the tibial head diameter and were no more statistically significant. The interindividual variability was reduced after normalisation to these two parameters, the body weight being more effective. We did not observe sex-specific differences in the percentage of the total cartilage volume taken up by the various joint surfaces. Our results suggest that, in young individuals without cartilage lesions, there exist sex-specific differences of the cartilage volume in the knee joint. However, these can be explained in terms of general differences in body constitution (body weight and bone size), without further significant influences of the sex. The knowledge of the normal, sex-specific cartilage volume is relevant when attempting to estimate the amount of tissue loss at the time at which symptoms occur in a patient with degenerative joint disease.

Adult↗

Repeatability of patellar cartilage thickness patterns in the living, using a fat-suppressed magnetic resonance imaging sequence with short acquisition time and three-dimensional data processing.

A fast, reproducible, and noninvasive method is required for quantifying cartilage thickness clinically and for studying the deformation of articular cartilage during and after mechanical loading in vivo. The objective of the current investigation was to test the repeatability of regional distribution patterns of patellar cartilage thickness in the living on the basis of a fat-suppressed magnetic resonance imaging sequence with a short acquisition time and three-dimensional digital data processing. The knees of eight healthy volunteers were transversally imaged with a fat-suppressed FLASH-3D (fast low angle shot) sequence (acquisition time: 4 minutes and 10 seconds). In each case, the joint was newly positioned before each of the six replicate measurements was taken. The patellar cartilage was reconstructed three-dimensionally, and the distribution of cartilage thickness was determined with a three-dimensional minimal-distance algorithm. Whereas the cartilage volume ranged from 3,198 to 7,149 mm3, the mean coefficient of variation for the 6-fold volume measurement was 1.35%. On average, 75.1% (+/- 4.1%) of all test pixels could be attributed to the same cartilage thickness interval (0.5 mm) by image analysis; 14.8% (+/- 2.4%) deviated by one interval; 6.6% (+/- 1.5%), by two intervals; and 3.5% (+/- 1.8%), by more than two intervals. We conclude that, on the basis of a magnetic resonance imaging sequence with an acquisition time of less than 5 minutes, the quantitative distribution of cartilage thickness can be determined with high precision in vivo.

Adult↗

Multidisciplinary predialysis programs: quantification and limitations of their impact on patient outcomes in two Canadian settings.

A 1993 National Institutes of Health Consensus statement stressed the importance of early medical intervention in predialysis populations. Given the need for evidence-based practice, we report the outcomes of predialysis programs in two major Canadian cities. The purpose of this report was to determine whether the institution of a multidisciplinary predialysis program is of benefit to patients, and to analyze those factors that are important in actualizing those benefits. Data from two different studies is presented: (1) a prospective, nonrandomized cohort study comparing patients who were or were not exposed to an ongoing multidisciplinary predialysis team (St Paul's Hospital) and (2) a retrospective review of outcomes before and after the institution of a predialysis program (The Toronto Hospital). Although created independently in major academic centers in Canada, the programs both aimed to reduce urgent dialysis starts, improve preparedness for dialysis, and improve resource utilization. The Vancouver study was able to demonstrate significantly fewer urgent dialysis starts (13% v 35%; P < 0.05), more outpatient training (76% v 43%; P < 0.05), and less hospital days in the first month of dialysis (6.5 days v 13.5 days; P < 0.05). Cost savings of the program patients in 1993 are conservatively estimated to be $173,000 (Canadian dollars) or over $4,000 per patient. The Toronto study demonstrated success in predialysis access creation (86.3% of patients), but could not realize any benefit in terms of elective dialysis initiation due to well-documented hemodialysis resource constraints. We conclude that an approach to predialysis patients involving a multidisciplinary team can have a positive impact on quantitative outcomes, but essential elements for success include (1) early referral to a nephrology center, (2) adequate resources for dedicated predialysis program staff and infrastructure, and (3) available resources for patients with end-stage renal disease (ESRD) (dialysis stations). In times of economic constraints, objective data are necessary to justify resource-intensive proactive programs for patients with ESRD. Future studies should confirm and extend our observations so that optimum and cost-effective care for patients approaching ESRD is uniformly available.

Canada↗

[Three-dimensional thickness and volume measurements of the knee joint cartilage by MR tomography: reproducibility in volunteers].

OBJECTIVE: To determine the reproducibility of three-dimensional volume and thickness measurements of the knee joint cartilage with MRI in volunteers. METHODS: The knees of 7 healthy individuals (ages 23 to 58 yrs.) were sagittally imaged with a resolution of 2 x 0.31 x 0.31 mm3, using a fat-suppressed FLASH-3 D sequence. The knee was repositioned in between replicate acquisitions, 6 data sets being obtained in each case. After semiautomatic segmentation and three-dimensional reconstruction of the cartilage, the thickness was determined independent of the original section orientation. The coefficient of variation for repeated volume measurements and the deviations of the maximal cartilage thickness values were calculated subsequently. RESULTS: The mean variation of the cartilage volumes of the replicate measurements was 1.4% (+/- 0.8%) in the patella, 1.7% (+/- 1.5%) in the femur, 3.0% (+/- 1.2%) in the medial tibial plateau and 3.5% (+/- 2.0%) in the lateral tibial plateau. The comparison of the distribution patterns of cartilage thickness yielded a high degree of agreement. Only in rare cases deviations of more than 0.5 mm were observed. CONCLUSIONS: The results show that the presented method for determining the quantitative distribution of articular cartilage yields a high degree of precision. It offers new possibilities in screening risk groups, monitoring the course of degenerative joint disease and the investigation of functional adaptation of the cartilage to mechanical loading.

Adult↗

Synthesis of the highly selective Na+/H+ exchange inhibitors cariporide mesilate and (3-methanesulfonyl-4-piperidino-benzoyl) guanidine methanesulfonate.

The syntheses of cariporide mesilate ((4-isopropyl-3-methanesulfonyl-benzoyl) guanidine methanesulfonate, HOE 642, CAS 159138-81-5), currently being clinically investigated as a protective drug in cardiac ischemia and reperfusion states, and of HOE 694 ((3-methanesulfonyl-4-piperidino-benzoyl)guanidine methanesulfonate, CAS 149725-40-6), widely used as a physiological and pharmacological research tool in studies comprising Na+/H+ exchange (NHE) inhibition, are described. Additionally, their selectivity on the different subtypes is disclosed.

Amiloride↗

Dynamic aspects of DNA/protein interactions in the transcriptional initiation complex and the hormone-responsive domains of the phosphoenolpyruvate carboxykinase promoter in vivo.

Transcription initiation of the gene encoding phosphoenolpyruvate carboxykinase (PEPCK) is stimulated by glucocorticoids and glucagon, via cAMP, and dominantly inhibited by insulin in rat liver and H4IIE cells. Lysolecithin-permeabilized H4IIE cells recover completely and continue to multiply, yet are transiently penetrable by macromolecules. These cells, after various hormonal treatments, were utilized for in situ DNase I protection studies of the PEPCK promoter. Nearly all of the sites of protein interaction observed in vitro are protected in vivo as well as several additional sites. The DNase I protection pattern is the same in cells without or with any of the hormone treatments, suggesting that hormonal modulation of transcription does not involve addition or removal of factors from the hormone response elements of the promoter. We focused on the organization and stability of the transcription initiation complex as well as the dynamic nature of distal promoter factors in their interaction with DNA. The transcription initiation complex was detected, and it appears to be co-existent with a short region of naked single-stranded DNA over the TATA box on the template strand, as determined by potassium permanganate reactivity. This complex is quite stable, even under conditions of much reduced RNA synthesis, which suggests that the complex is not broken down and reformed with each round of initiation by RNA polymerase II. Other factors bind to the PEPCK promoter with half-lives ranging from a few minutes to more than 40 min. The cAMP response element apparently involves transcriptional modulation achieved through modification of a bound factor (presumably cAMP response element-binding protein), whereas the glucocorticoid/insulin-responsive region of the promoter functions through factors which are involved in a rapid exchange, suggesting quite different modes of transcriptional regulation.

Animals↗

Characterization of the factors binding to a PEPCK gene upstream hypersensitive site with LCR activity.

A previously described upstream hypersensitive site (HS) in the PEPCK gene at -4800 bp, termed HS A (1), has been characterized and determined to bind at least two factors. One of these is a member of the ubiquitous CREB/ATF family, and the second is a novel tissue specific protein, pep A. A construct carrying HS A and the PEPCK proximal promoter was tested in transgenic mice and its CAT activity compared to the proximal promoter alone. The HS A was shown to drive tissue-specific, position-independent transcription of the CAT reporter gene 2-3 fold more effectively than the proximal promoter alone, with a concommitant 4-5 fold higher expression of CAT. Protein binding activity has been localized to a 33 bp region. This region contains a CRE (2) which is shown to bind a member of the CREB/ATF family through competition assays with an oligo containing a CRE from the proximal promoter and by the appearance of a supershift when the factor/oligo complex was exposed to CREB polyclonal antibody. Through restriction enzyme digests and competition of protein binding with an oligonucleotide homologous to HS A with a mutated CRE we have characterized a putative binding site for a liver-specific factor. In vitro and 'in vivo' footprinting studies complement each other, as well as, mobility shift assay data in designating the binding site of the proteins. The CREB/ATF factor and Pep A bind independently of each other during short term incubations, however, both factors can be accomodated on the DNA substrate as a function of extended time of incubation. Preliminary biochemical analysis defines the subunit molecular mass of the CREB/ATF like proteins at 55, 42, and 35 kD, while the tissue specific material exists as a single homogeneous subunit polypeptide in SDS of molecular mass = 49 kD.

Animals↗

Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome.

Colonic motor activity and plasma concentrations of cholecystokinin (CCK) both increase after oral intake of a meal. Thus, CCK had been thought to mediate the postprandial increase in colonic motor activity, which is termed gastrocolonic response. The present study used the substance loxiglumide, which acts as a specific antagonist at the CCK-A receptor, to evaluate this hypothesis. In the first set of experiments, eight healthy subjects were studied four times on separate days. A multilumen catheter was endoscopically placed with its tip lying in the descending colon. Motor activity was recorded by a low-compliance perfusion manometry system at six locations 60-45 cm from the anus. Basal activity was recorded for at least 2 hours to achieve steady-state conditions. The order of the following four experiments was randomized: (a) intravenous infusion of the CCK analogue cerulein at increasing doses (7.5, 15, 30, and 60 ng/kg.h, each given for 30 minutes); (b) intravenous cerulein plus 5 mg/kg.h loxiglumide; (c) a 1000-kcal solid/liquid meal consisting of regular German food; and (d) a meal plus 5 mg/kg.h loxiglumide. In the second set of experiments, eight patients with irritable bowel syndrome were studied twice on two separate days, and two experiments were performed n randomized order: (a) a 1000-kcal solid/liquid meal consisting of regular German food; or (b) a meal plus 5 mg/kg.h loxiglumide. The motor index was calculated as the area under contractions by a computerized system. The 1000-kcal meal markedly increased colonic motor activity. This gastrocolonic response was significantly greater in patients with irritable bowel syndrome than in healthy volunteers. Cerulein stimulated motor activity only at pharmacological doses (30-60 ng/kg.h), which resulted in plasma CCK levels markedly exceeding postprandial values. Loxiglumide abolished the effects of cerulein even at pharmacological doses. However, loxiglumide did not inhibit the gastrocolonic response to a regular meal either in healthy volunteers or in patients with irritable bowel syndrome. Loxiglumide also failed to alter the interdigestive colonic motor activity. Therefore, effects mediated by the CCK-A receptor do not play a major physiological role in the regulation of the interdigestive and postprandial motility of the left colon.

Adult↗

The interplay of ubiquitous DNA-binding factors, availability of binding sites in the chromatin, and DNA methylation in the differential regulation of phosphoenolpyruvate carboxykinase gene expression.

We have identified DNA elements in the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter which are bound 'in vivo' by proteins under conditions of basal level gene expression and have evaluated several hypothesis to account for the tissue specific expression of the gene. In vitro DNase I footprinting demonstrated that factors which bind to basal expression elements of the PEPCK promoter, the BSE/CRE and NFI/CCAAT sites, are also present in HTC and XC cells which do not express the PEPCK gene. 'In vivo' DNase I footprinting demonstrated that the BSE/CRE, NFI/CCAAT, and three additional sites are bound by protein in H4IIE cells which express the PEPCK gene but not in the HTC or XC cells. No evidence for a repressor protein or for phased nucleosome binding to the PEPCK promoter in HTC or XC cells could be detected. Genomic sequencing was used to determine if differential methylation of the PEPCK promoter could account for the lack of factor binding in HTC and XC nuclei. None of the 14 cytosine residues in CpG dinucleotides was methylated in H4IIE or rat liver DNA, all were methylated in rat sperm DNA, and 6 were methylated in HTC DNA; including the cytosine at position--90 within the BSE/CRE. Only one cytosine residue, at position--90, was methylated in XC DNA. Treatment of XC cells with 5-azacytidine resulted in loss of methylation at the--90 position yet this was insufficient to allow synthesis of a detectable amount of PEPCK mRNA.

Animals↗

[Not Available].

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Adolescent↗

Specific nuclear proteins interact with the Rous sarcoma virus internal enhancer and share a common element with the enhancer located in the long terminal repeat of the virus.

We have documented that the Rous sarcoma virus (RSV) internal enhancer functions in the nontransformed Baby Hamster Kidney (BHK) cell line. The sequences within this region were assayed for their ability to bind to specific factors present in BHK nuclear extracts using the gel retardation assay and DNAse I footprinting. At least two sequences within the internal enhancer which can specifically bind nuclear factors in vitro have been identified. These regions are located between nucleotides 813-850 and 856-877. These sites map within the overall region of the internal enhancer which has been shown to be essential for enhancer activity and within the specific region which can function as an orientation independent enhancer. Using the DNase I footprinting and binding data to design an oligonucleotide, we have demonstrated that an oligonucleotide extending from nucleotides 804-877 will substitute efficiently as an enhancer. We also demonstrate that the SV40 enhancer does not compete for the factors which bind to the RSV internal enhancer, whereas an oligonucleotide to the binding site for EFII in the LTR can compete for factor binding to the internal enhancer.

Animals↗

Herpes simplex virus immediate early infected-cell polypeptide 4 binds to DNA and promotes transcription.

In herpes simplex virus (HSV)-infected cells, there is a sequential expression of viral genes. In vivo experiments have implicated the Mr 175,000 immediate early protein ICP4 (infected-cell polypeptide 4) in the regulation of viral RNA synthesis, but the mechanism whereby ICP4 regulates transcription of viral genes is at present unknown. In this report we describe experiments with an in vitro transcription system and a purified preparation of ICP4 (estimated 5% of total protein). Using DNA from the HSV glycoprotein D gene (gD) as the template, we have observed that specific binding occurs between ICP4 and DNA sequences adjacent to the gD gene promoter and ICP4 stimulates initiation of transcription from the gD gene. The degree of stimulation depends on the amount of ICP4 present in the incubation. The kinetics of RNA synthesis demonstrate that the protein acts at the initiation step of transcription. These results identify ICP4 as a viral transcription factor whose presence on DNA facilitates the formation of transcription complexes.

Animals↗

[Approaches to reduce the retroaction of long-term monitoring of bioelectric events in ergonomic field studies (author's transl)].

When monitoring bioelectric signals the surface electrodes can cause a retroaction on the subject thereby introducing an error of measurement. There are two types of retroaction: physical and psycho-physiological. A physical retroaction due to the hydration process of the skin occurs if 'wet' electrodes are used for the recording of the skin conductance level (SCL) causing a continuous drift of the SCL and a decrease in sensitivity to SCL changes. Therefore a dry electrode was developed with improved performance: It exhibits less sensitivity to motion, is not subject to polarization, and features better SCL long-term stability. When recording the electrocardiogram or the electromyogram a psychophysiological retroaction occurs due to the annoyance caused by the skin-irritating abrading techniques in order to decrease the skin impedance and reduce the motion artifact. In an attempt to abandon the skin preparation whenever permissible without sacrificing the measurement accuracy a performance estimation procedure was developed. Basing on the information on the signal frequency content, the electrode contact area, the required accuracy of measurement and the amplifier input impedance a decision on the necessity of skin preparation is made. Moreover, the results of a study are reported investigating the reduction of motion artifacts by means of electrode design and appropriate electrode jelly formulation.

Electrocardiography↗

Predictability of the size of laser-induced lesions in T1-Weighted MR images obtained during interstitial laser-induced thermotherapy of benign prostatic hyperplasia.

The purpose of this study was to predict diameters of lesions induced by laser-induced thermotherapy (LITT) of benign prostatic hyperplasia (BPH) from MRI signal/tissue temperature correlations during on-line monitoring with a temperature-sensitive fast low-angle shot (FLASH) sequence. Twenty LITT procedures with Nd:YAG (1,064 nm) and diode (830 nm) lasers were monitored on line with a T1-weighted FLASH sequence at 1.5 Tesla. Interstitial prostate temperature (T) was measured on line in 10 LITT procedures and laser energy deposition in 12. Slopes of linear regression curves for signal intensity (SI) over T were applied to determine SI at 60 degrees C to estimate diameters of intraprostatic LITT lesions. Diameters of unperfused LITT lesion cores in contrast-enhanced T1-weighted images served as gold standards. Linear regression curves with an average slope of -.54% SI/degrees C were obtained in 17 LITT procedures. Correlation coefficients were r = .92-.95 for SI/T and SI/energy deposition. Baseline variation of SI at body temperature was +/-3.9%, corresponding to +/-7 degrees C. Prediction of size (13 lesions) from on-line FLASH imaging was correct in 10 of 13, whereas 3 lesions were overestimated. Prediction of LITT lesion diameters from on-line MRI monitoring is possible with a temperature-sensitive FLASH sequence in the prostate. Accuracy may suffice to assign target regions of interest to tissue locations to be protected from coagulation.

Aged↗

Original research: an investigation of life with end stage renal disease: sociocultural case studies analysis.

The goal of this research was to gain an integrated understanding of the lives of people with end stage renal disease (ESRD) requiring hemodialysis (HD)--one that included cultural, institutional and historical contexts. In this research a sociocultural analysis of four cases of everyday life with ESRD offered a situated understanding of life with this disease. This study revealed that life with ESRD is work. Moreover, while people living with ESRD do the bulk of that work, family also work to "live" with ESRD. Biomedically-based knowledge can be enriched by incorporating two relevant sources of knowledge: participants and participants' significant others. The addition of these sources of knowledge broadens health care practitioners' understanding of ESRD as it is "lived," and, so informed, practitioners can better provide the kinds of education and support that will enhance the lives of people with this illness.

Adaptation, Psychological↗