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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 127 records · Page 7Linked to original sources
PubMed2001

Rayleigh-Bénard percolation transition study of thermal convection in porous media: numerical simulation and NMR experiments.

Thermal convection was studied as a function of the porosity in random-site percolation model objects in a Rayleigh-Bénard configuration. NMR velocity mapping experiments and numerical simulations using the finite-volume method are compared. Velocity histograms were evaluated and can be described by power laws in a wide range. The maximum velocity as a function of the porosity indicates a combined percolation/Rayleigh-Bénard transition.

Journal Article↗
PubMed2001

Flow through percolation clusters: NMR velocity mapping and numerical simulation study.

Three- and (quasi-)two-dimensional percolation objects have been fabricated based on Monte Carlo generated templates. The object size was up to 12 cm (300 lattice sites) in each dimension. Random site, semicontinuous swiss-cheese, and semicontinuous inverse swiss-cheese percolation models above the percolation threshold were considered. The water-filled pore space was investigated by nuclear magnetic resonance (NMR) imaging and, after exerting a pressure gradient, by NMR velocity mapping. The spatial resolutions of the fabrication process and the NMR experiments were 400 microm and better than 300 microm, respectively. The experimental velocity resolution was 60 microm/s. The fractal dimension, the correlation length, and the percolation probability can be evaluated both from the computer generated templates and the corresponding NMR spin density maps. Based on velocity maps, the percolation backbones were determined. The fractal dimension of the backbones turned out to be smaller than that of the complete cluster. As a further relation of interest, the volume-averaged velocity was calculated as a function of the probe volume radius. In a certain scaling window, the resulting dependence can be represented by a power law, the exponent of which was not yet considered in the theoretical literature. The experimental results favorably compare to computer simulations based on the finite-element method (FEM) or the finite-volume method (FVM). This demonstrates that NMR microimaging as well as FEM/FVM simulations reliably reflect transport features in percolation clusters.

Journal Article↗
PubMed2001

Quality of hospital care for seriously ill children in less-developed countries.

BACKGROUND: Improving the quality of care for sick children referred to hospitals in less-developed countries may lead to better outcomes, including reduced mortality. Data are lacking, however, on the quality of priority screening (triage), emergency care, diagnosis, and inpatient treatment in these hospitals, and on aspects of these potential targets that would benefit most from interventions leading to improved health outcomes. METHODS: We did a qualitative study in 13 district hospitals and eight teaching hospitals in seven less-developed countries. Experienced paediatricians used a structured survey instrument to assess initial triage, emergency and inpatient care, staff knowledge and practices, and hospital support services. FINDINGS: Overall quality of care differed between countries and among hospitals and was generally better in teaching hospitals. 14 of 21 hospitals lacked an adequate system for triage. Initial patient assessment was often inadequate and treatment delayed. Most emergency treatment areas were poorly organised and lacked essential supplies; families were routinely required to buy emergency drugs before they could be given. Adverse factors in case management, including inadequate assessment, inappropriate treatment, and inadequate monitoring occurred in 76% of inpatient children. Most doctors in district hospitals, and nurses and medical assistants in teaching and district hospitals, had inadequate knowledge and reported practice for managing important childhood illnesses. INTERPRETATION: Strengthening care for sick children referred to hospital should focus on achievable objectives with the greatest potential benefit for health outcome. Possible targets for improvement include initial triage, emergency care, assessment, inpatient treatment, and monitoring. Priority targets for individual hospitals may be determined by assessing each hospital.

Adolescent↗
PubMed2001

The physiological basis of conduction slowing in ALS patients homozygous for the D90A CuZn-SOD mutation.

Familial amyotrophic lateral sclerosis (ALS) with the autosomal-recessively inherited D90A CuZn-superoxide dismutase (CuZn-SOD) mutation is characterized by a stereotypic slowly progressive, distinctive phenotype and very slow central motor conduction. To determine the basis of this slowing, we assessed corticomotoneuronal function using peristimulus time histograms (PSTHs) in 8 ALS patients homozygous for the D90A CuZn-SOD mutation. The results were compared with findings in 10 patients with multiple sclerosis (MS), in which slowing of central motor conduction is common, and 11 healthy subjects. PSTHs were constructed from 3-7 different, voluntarily recruited motor units recorded in each patient from the extensor digitorum communis muscle (EDC). In D90A and MS patients, the stimulus threshold, onset latency, number of excess bins, duration, amplitude, and synchrony of the primary peak differed significantly from controls (P < 0.0004). The mean onset latency of the primary peak in D90A patients was 35.3 ms, compared to 23.6 ms for MS patients and 19.3 ms for normal subjects (P < 0.0001). In the D90A patients, the onset latencies of the primary peak had a bimodal distribution, whereas in MS the distribution showed a continuum. Loss of synchrony was similar in D90A and MS patients, but the threshold, number of excess bins, and duration differed significantly (P < 0.0057), which suggests that either axonal loss or demyelination can result in delayed and desynchronized primary peaks. We propose that conduction slowing in the D90A homozygotes results from selective loss of fast-conducting large pyramidal cells with preservation of slow-conducting mono- or polysynaptic corticomotoneuronal connections.

Adult↗
PubMed2001

The motor cortex and amyotrophic lateral sclerosis.

On theoretical grounds, abnormalities of the motor cortex in patients with amyotrophic lateral sclerosis (ALS) could lead to anterograde ("dying-forward") transneuronal degeneration of the anterior horn cells as suggested by Charcot. Conversely, retrograde ("dying-back") degeneration of the corticospinal tracts could affect the motor cortex. Evidence derived from clinical, neuropathological, static, and functional imaging, and physiological studies, favors the occurrence of anterograde degeneration. It is hypothesized that transneuronal degeneration in ALS is an active excitotoxic process in which live but dysfunctional corticomotoneurons, originating in the primary motor cortex, drive the anterior horn cell into metabolic deficit. When this is marked, it will result in more rapid and widespread loss of lower motor neurons. In contrast, slow loss of corticomotoneurons, as occurs in primary lateral sclerosis (PLS), precludes excitotoxic drive and is incompatible with anterograde degeneration. Preservation of slow-conducting non-M1 direct pathways in PLS is not associated with excitotoxicity, and anterior horn cells survive for long periods of time.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Reduction in intestinal leukocyte adherence in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.

OBJECTIVES: To investigate leukocyte adherence in intestinal venules in experimental endotoxemia after treatment with the 21-aminosteroid U-74389G. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory. SUBJECTS: Twenty-one male Wistar rats weighing 190 +/- 40 g. INTERVENTIONS: The rats were divided equally into three groups: (a) control group, (b) endotoxemia (5 mg/kg lipopolysacharide from Escherichia coli O55:B5), and (c) endotoxemia and U-74389G administration 30 min before (3 mg/kg) and 60 min after endotoxin challenge (1.5 mg/ kg). MEASUREMENTS AND MAIN RESULTS: The distal small intestine of the animals was examined using intravital fluorescence videomicroscopy 2 h after endotoxin challenge. Leukocytes were stained in vivo by means of rhodamine 6G. In the endotoxemic animals we observed a fourfold increase in the count of firmly adherent leukocytes in submucosal post-capillary and collecting venules. Treatment with the 21-aminosteroid U-74389G significantly attenuated the count of sticking leukocytes in the collecting venules (control, 61 +/- 10 cells/mm2; lipopolysaccharide, 237 +/- 42 cells/mm2; U-74389G 125 +/- 9 cells/mm2; p < 0.05). In these venules leukocyte rolling behavior was comparable to that in the control group without endotoxin challenge. CONCLUSIONS: Administration of U-74389G, which has radical scavenging properties, attenuates leukocyte adherence in selected populations of intestinal venules which is found increased during endotoxemia. Thus, 21-aminosteroids may have an impact in the treatment of endotoxin-induced intestinal injury.

Animals↗
PubMed2001

Spontaneous volume changes in gastric banding devices: complications of a semipermeable membrane.

The goal of this study was to prove that adjustable laparoscopic gastric banding (LAP-BAND) is semipermeable and that luminal adjustment with saline leads to spontaneous fluid loss, luminal widening, and effect loss which makes repeated readjustments necessary. In 64 patients stoma adjustment was performed with saline according to the guidelines of the manufacturer (group 1). In 32 patients hyperosmolar contrast material was used for stoma readjustments with the intention to detect a system leakage after spontaneous fluid loss and spontaneous luminal widening was observed (group 2). After spontaneous luminal narrowing had occurred in group 2, all patients from group 2 and all additional patients (n = 148) underwent stoma (re-) adjustment with iso-osmolar contrast material (group 3). Spontaneous fluid changes which led to spontaneous changes of the luminal width were then analyzed for the different filling substances in each group. Fifty-two patients from group 1 presented with effect loss because a spontaneous luminal widening had occurred secondary to a fluid loss of 0.1-0.2 ml/month. All 32 patients from group 2 presented with increasing obstruction and food intolerance because a spontaneous luminal narrowing had occurred secondary to a spontaneous fluid gain of 0.1-0.3 ml/month. In our patients from group 3, where stoma adjustment was performed with iso-osmolar contrast material, no spontaneous fluid changes were observed and luminal width/degree of obstruction did not change. The LAP-BAND is semipermeable. Stoma adjustment should not be performed with saline in order to avoid spontaneous luminal widening and the need for repeated readjustments. Stoma adjustments with hyperosmolar contrast material are clearly contraindicated since osmotic fluid gain leads to increasing obstruction. Stoma adjustments should be performed using iso-osmolar filling media which provide a stable luminal obstruction.

Contrast Media↗
PubMed2001

Mutational analysis of INI1 in sporadic human brain tumors.

The INI1/SMARCB1/hSNF5 gene on chromosome 22 is frequently mutated in rhabdoid tumors. An association of INI1 mutations with allelic losses on chromosome 22 supports a classical tumor suppressor mechanism. Several brain tumor entities including astrocytomas, glioblastomas and ependymomas are characterized by allelic losses on chromosome 22. In the present study we examined a series of 200 brain tumors by Single-strand conformation polymorphism analysis and direct sequencing for point mutations in INI1. In addition, all tumors were analyzed for homozygous deletions spanning both exons 3 and 8 of INI1. No mutations or homozygous deletions were detected in astrocytomas, glioblastomas, oligodendroglial tumors, neurinomas or medulloblastomas. However, a point mutation could be identified in the single case of plexus carcinoma. Our data suggest that INI1 mutations are involved in the pathogenesis of plexus carcinoma; however, INI1 alterations are not a frequent event in the majority of brain tumor entities.

Base Sequence↗
PubMed2001

Multicenter evaluation of an automated system using selected bacteria that harbor challenging and clinically relevant mechanisms of resistance to antibiotics.

A multicenter study was carried out to evaluate the performance of a new commercial automated system in comparison with that of the reference agar dilution method. Ten clinical microbiology laboratories tested a collection of 61 strains of gram-negative bacilli (49 Enterobacteriaceae and 12 Pseudomonas aeruginosa), and 6 other laboratories tested a collection of 55 strains of gram-positive cocci (10 enterococci and 45 staphylococci) against 10-20 antimicrobial agents. The strains were selected on the basis that they harbored challenging and characterized mechanisms of resistance. In comparison with the agar reference method, the automated system gave an overall essential agreement (+/-1 dilution) of 94.5%, 93.5%, and 97% for the gram-negative bacilli, enterococci, and staphylococci, respectively. According to the interpretive standards of the National Committee for Clinical Laboratory Standards, the category agreement ranged from 96 to 96.4% for the three sets of organisms. The accuracy of the automated system, as determined by the kappa test, ranged from 0.80 to 0.88, reflecting an almost perfect agreement with the reference technique. Very major, major, and minor errors obtained with the automated system were 0.3%, 2.9%, and 6.6% for gram-negative bacilli, 3.4%, 0%, and 5% for enterococci, and 1%, 1.6%, and 2.7% for staphylococci, respectively. The high rate of very major errors in enterococci was mostly due to a single strain of multidrug-resistant Enterococcus faecium, which was found susceptible to several antibiotics in a majority of participant laboratories. The use of a heavy inoculum and of a broth test medium by the automated system might account for a better expression of certain resistance mechanisms, including beta-lactamases, as compared to the agar dilution reference method. The interlaboratory reproducibility was acceptable, as shown by the narrow dispersion of MICs and by the results of quality control.

Anti-Bacterial Agents↗
PubMed2001

Modeling epidemics caused by respiratory syncytial virus (RSV).

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in children. In this paper we use models of RSV transmission to interpret the pattern of seasonal epidemics of RSV disease observed in different countries, and to estimate epidemic and eradication thresholds for RSV infection. We compare the standard SIRS model with a more realistic model of RSV transmission in which individuals acquire immunity gradually after repeated exposure to infection. The models are fitted to series of monthly hospital case reports of RSV disease from developed and developing countries. The models can explain many of the observed patterns: regular yearly outbreaks in some countries, and in other countries cycles of alternating larger and smaller annual epidemics, with shifted maxima in alternate years. Previously these patterns have been attributed to the transmission of different strains of RSV. In some countries the timing of epidemics is not consistent with increased social contact among school children during term time being the major driving mechanism. Climatic factors appear to be more important. Qualitatively different models gave equally good fits to the data series, but estimates of the transmission parameter were different by a factor of 4. Estimates of the basic reproduction number (R(0)) ranged from 1.2 to 2.1 with the SIRS model, and from 5.4 to 7.1 with the model with gradual acquisition of partial immunity.

Child↗
PubMed2001

Facilitated neurogenic inflammation in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is characterized by a variety of clinical features including spontaneous pain and hyperalgesia. Increased neuropeptide release from peripheral nociceptors has been suggested as a possible pathophysiologic mechanism triggering the combination of trophic changes, edema, vasodilatation and pain. In order to verify the increased neuropeptide release in CRPS, electrically induced neurogenic vasodilatation and protein extravasation were evaluated in patients and controls. We performed a prospective study on 10 patients with acute and untreated CRPS and 10 matched healthy controls. Neurogenic inflammation was elicited by strong transcutaneous electrical stimulation via intradermal microdialysis capillaries which simultaneously enabled measurement of protein extravasation. Laser-Doppler scanning was used to assess axon reflex vasodilatation. Axon reflex vasodilatation was significantly increased in CRPS patients (438 +/- 68% of baseline vs. 306 +/- 52%; P < 0.05) and transcutaneous electrical stimulation provoked protein extravasation only in the patients (before, 0.28 +/- 0.03 mg/ml; during stimulation, 0.34 +/- 0.04 mg/ml), whereas protein concentration steadily declined during stimulation in the healthy controls (before, 0.23 +/- 0.04 mg/ml; during stimulation, 0.18 +/- 0.04; P < 0.001). The time course of electrically induced protein extravasation in the patients resembled the one observed following application of exogenous substance P (SP). We conclude that neurogenic inflammation is facilitated in CRPS. Our results suggest an increased releasability of neuropeptides in CRPS.

Adult↗
PubMed2001

Bactericidal properties of the chloroform fraction from rhizomes of Aristolochia paucinervis Pomel.

The deffated chloroform fraction (APRC) obtained from the rhizomes of Aristolochia paucinervis Pomel (Aristolochiaceae) has a high bacteriostatic activity against bacterial strains like Clostridium perfringens ATCC 13124 and Enterococcus faecalis ATCC 29212. Here, we report the bactericidal activity of APRC against both strains which was evaluated by using time-to kill assays. The results showed that APRC produced an intense time-dependent bactericidal effect against C. perfringens, achieving over a 24 h-period a 5log10-unit decrease in CFU/ml at a concentration > or =1.25 x MIC. In contrast, when tested against E. faecalis, APRC exhibited a concentration-dependent killing activity at concentrations of 1.25 x MIC and 2.5 x MIC, yielding to a decrease of 1.5 and 2.5log10-unit in CFU/ml at 4 h, respectively. However, substantial regrowth of E. faecalis occurred within 24 h. Ultrastructural alterations were observed for both exposed microorganisms by scanning and transmission electron microscopy.

Anti-Bacterial Agents↗
PubMed2001

Arterial compliance abnormalities in isolated systolic hypertension.

Arterial compliance measurements using intraarterial pulse contour analysis and a modified Windkessel model were carried out in 19 patients with isolated systolic hypertension (> or = 160/< or = 90 mm Hg) and compared to measurements in 29 patients with essential hypertension (diastolic blood pressure [BP] > or = 95 mm Hg) and 47 normotensive control subjects. Arterial capacitive compliance was significantly lower in isolated systolic hypertension than in essential hypertension (P < .0002) and significantly lower in essential hypertension than in normotensive control subjects (P < .0001). Although the isolated systolic hypertension group was older than the essential hypertension group, the reduction of capacitive compliance in isolated systolic hypertension persisted even when comparison was made with a more nearly age-matched group of essential hypertension. In contrast, oscillatory compliance was reduced similarly in isolated systolic hypertension and essential hypertension compared to normotensive control subjects (P < .0001). Although pulse pressure was greater in isolated systolic hypertension than in essential hypertension, only a weak correlation (r = -0.34) existed between pulse pressure and capacitive compliance. These data indicate that both essential hypertension and isolated systolic hypertension patients exhibit comparably abnormal structure or tone of the small vessels that are the site of oscillations or reflections in the arterial vasculature. In isolated systolic hypertension there is a profound reduction in large artery or capacitive compliance that accounts for the increase in systolic BP and decrease in diastolic BP. This abnormality cannot be accurately assessed by pulse pressure alone.

Aged↗
PubMed2001

Extensive tissue-specific variation of allelic methylation in the Igf2 gene during mouse fetal development: relation to expression and imprinting.

The imprinted Igf2 gene is active only on the paternal allele in most tissues. Its imprinting involves a cis-acting imprinting-control region (ICR) located upstream of the neighboring and maternally expressed H19 gene. It is thought that differential methylation of the parental alleles at the ICR is crucial for parental imprinting of both genes. Differentially methylated regions (DMRs) have also been identified within the Igf2 gene and their differential methylation is thought to be established during early development. To gain further insight into the function of these DMRs, we performed a quantitative analysis of their allelic methylation levels in different tissues during fetal development and the postnatal period in the mouse. Surprisingly, we found that the methylation levels of Igf2 DMRs vary extensively during fetal development, mostly on the expressed paternal allele. In particular, in skeletal muscle, differential allelic methylation in both DMR 1 and DMR 2 occurs only after birth, whereas correct paternal monoallelic expression is always observed, including in the embryonic stages. This suggests that differential methylation in the DMR 1 and DMR 2 of the Igf2 gene is dispensable for its imprinting in skeletal muscle. Furthermore, progressive methylation of the Igf2 paternal allele appears to be correlated with concomitant postnatal down-regulation and silencing of the gene. We discuss possible relations between Igf2 allelic methylation and expression during fetal development.

Age Factors↗
PubMed2001

A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice.

Bone resorption is a dominant feature of many bone metastases and releases factors from the bone matrix that can promote the expression of the metastatic phenotype in cancer cells. Since proteolytic enzymes, including matrix metalloproteinases (MMPs) contribute to bone destruction by metastatic tumour cells and host cells, we have examined the effect of a MMP inhibitor, batimastat, on the ability of MDA-MB-231 cells to degrade bone in vitro and to form bone metastases in BalbC nu/nu mice. In vitro, the neoplastic cells produced MMP-2 and MMP-9, degraded [3H]-proline-labelled osteoblast matrices, and formed resorption pits in cortical bone. These phenomena were inhibited by < or = 20 microM batimastat. To induce vertebral and long bone metastases in vivo, 1x10(5) MDA-MB-231 cells were injected into the arterial circulation of BalbC nu/nu mice. Test groups were also given 30 mg/kg batimastat intraperitoneally (i.p.). After 21 days, the long bone metastases were characterised by a 67% reduction of metaphyseal medullary bone and complete replacement of marrow by tumour. In tumour-bearing mice that had been treated with 30 mg/kg batimastat i.p., the tumour volume decreased 8-fold, osteolysis was inhibited by 35%, and replacement of the bone marrow by tumour was inhibited by 65%. Similar effects were observed in the vertebral metastases. These data provide evidence that MDA-MB-231 cells can degrade osteoblast matrices and mineralised bone in vitro and support the hypothesis that MMPs are involved in the pathogenesis of osteolytic bone metastases in vivo. They demonstrate that an agent which inhibits proteolysis can retard the development of osteolytic bone metastases in this model.

Animals↗
PubMed2001

Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats.

Attempts to condition fear potentiation of startle (FPS) in rats younger than 23 days of age have not been successful, regardless of the type of aversively conditioned stimulus used (P. S. Hunt, R. Richardson, & B. A. Campbell, 1994; R. Richardson, G. Paxinos, & J. Lee, 2000; R. Richardson & A. Vishney, 2000). In the present study, the authors report that peripheral injections of strychnine hydrochloride, a glycine receptor antagonist, and intracerebroventricular infusions of corticotropin releasing hormone (CRH) both potentiated the acoustic startle response (ASR) in 16-18-day-old rats. Because strychnine and CRH have distinct sites of activation in the primary startle pathway, it can be concluded that this pathway is functional and modifiable in rats younger than 23 days of age. This finding suggests that the failure to observe conditioned FPS in preweanling rats is due to an immaturity of the secondary fear circuit responsible for enhancing the ASR during a fear state.

Age Factors↗