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Biomedical subjects

M Muller

Publications and source records attributed to M Muller.

At least 37 records · Page 2Linked to original sources

Non-destructive determination of local strain with 100-nanometre spatial resolution

Structure sizes of approximately 180 nm are now standard in microelectronics, and state-of-the-art fabrication techniques can reduce these to just a few tens of nanometres. But at these length scales, the strain induced at interfaces can locally distort the crystal lattice, which may in turn affect device performance in an unpredictable way. A means of non-destructively characterizing such strain fields with high spatial resolution and sensitivity is therefore highly desirable. One approach is to use Raman spectroscopy, but this is limited by the intrinsic approximately 0.5-microm resolution limit of visible light probes. Techniques based on electron-beam diffraction can achieve the desired nanometre-scale resolution. But either they require complex sample preparation procedures (which may alter the original strain field) or they are sensitive to distortional (but not dilational) strain within only the top few tens of nanometres of the sample surface. X-rays, on the other hand, have a much greater penetration depth, but have not hitherto achieved strain analysis with sub-micrometre resolution. Here we describe a magnifying diffraction imaging procedure for X-rays which achieves a spatial resolution of 100nm in one dimension and a sensitivity of 10(-4) for relative lattice variations. We demonstrate the suitability of this procedure for strain analysis by measuring the strain depth profiles beneath oxidized lines on silicon crystals.

Journal Article↗

Effect of surface penetrating sealant on surface texture and microhardness of composite resins.

The application of Fortify (Bisco, Lombard, IL), an unfilled resin, to the surface of composite resin restorations is intended to fill in defects in the surface that persist despite polishing, improve marginal integrity, and increase these materials' resistance to abrasion. The aim of this study was to observe the surface texture by scanning electron microscopy and measure the microhardness of the surface. For each sample of composite resin covered with glaze, 40 measurements were made of the thickness of the resin. Measurements of the Vickers microhardness included three samples of composite resin, three samples of glaze, and six samples of composite resin covered with glaze. A relationship was established between microhardness and thickness. Scanning electron microscopy showed a noticeable improvement in the surface texture. Nevertheless, areas were seen in which glaze seemed very thin or even completely absent. Measurements of the thickness ranged from 0-70 microm. The mean microhardness of composite resin was 65.8 +/- 0.7, while the mean hardness of glaze was 7.3 +/- 0.7. The microhardness of the double layer was reduced, depending on the thickness of the glazing resin. The capacity of glaze to mask surface defects of composite resin was shown, but it was difficult to obtain a regular surface with liquid resin. The application of this product caused a decrease of the microhardness of the composite resin's surface.

Composite Resins↗

Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D(3).

1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] inhibits production of IL-12, a cytokine involved in the development of Th1 cells and in the pathogenesis of Th1-mediated autoimmune diseases. Here, we show that 1,25(OH)(2)D(3) and a non-hypercalcemic analogue are selective and potent inhibitors of Th1 development in vitro and in vivo without inducing a deviation to the Th2 phenotype. Administration of 1,25(OH)(2)D(3) or its analogue prevents chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide 35 - 55 (MOG(35 - 55)) in Biozzi AB / H mice. The inhibition of EAE induction is associated with a profound reduction of MOG(35 - 55)-specific proliferation and Th1 cell development. Importantly, the non-hypercalcemic analogue also provides long-term protection from EAE relapses induced by immunization with spinal cord homogenate when administered for a short time at symptom onset or even after the first peak of disease. Neuropathological analysis shows a reduction of inflammatory infiltrates, demyelinated areas and axonal loss in brains and spinal cords of treated mice. These resuls indicate that inhibition of IL-12-dependent Th1 cell development is associated with effective treatment of CR-EAE and suggest the feasibility of an approach based on low molecular weight inhibitors of IL-12 production in the treatment of multiple sclerosis.

Animals↗

Aeromonas wound infection in burns.

Infection of burn patients with the Aeromonas organism is an uncommon event. This paper documents four cases of Aeromonas hydrophila and one case involving both A. hydrophila and A. caviae occurring in burn patients between 1990 and 1998 at the Royal Brisbane Hospital burns unit. The organism was isolated from either skin swabs, tissue samples, blood cultures or cultured lines. In all patients there was a history of immersion in water immediately post burn. There is one case of invasion and destruction of deeper tissues and one fatality. Appropriate management requires a high index of suspicion if a history of immersion in untreated water post burn is given and the treatment involves aggressive excision and antibiotic therapy.

Adult↗

Replication of yeast rDNA initiates downstream of transcriptionally active genes.

In the yeast S. cerevisiae, ARS (autonomously replicating sequence) elements located in the intergenic spacers of the rRNA gene locus are infrequently activated as origins of replication. We analyzed the rARS activation with a combination of neutral/neutral (N/N) two-dimensional (2D) gel electrophoresis and either the intercalating drug psoralen, which in vivo specifically marks the transcribing gene copies, or the selective accessibility of restriction sites in transcriptionally active genes. We found that initiation of replication starts at those rARSs placed immediately downstream of transcribing rRNA genes. This correlation between transcription and replication is consistent with the presence of nucleosome-free enhancers at each transcriptionally active gene copy and suggests that the transcription factor Abf1p is involved in replication initiation at the ARS in the rDNA gene locus.

DNA Replication↗

CARS microscopy with folded BoxCARS phasematching

Three-dimensional microscopy based on coherent anti-Stokes Raman scattering (CARS) is a powerful new imaging technique, in which the contrast arises from molecular vibrations. Based on a simple numerical model, it is shown how the CARS interaction volume depends on the focusing parameters and the type of phasematching used. Collinear phasematching yields an ellipsoidal interaction volume, with lateral dimensions that readily cause vignetting of the CARS signal emission at the collection microscope objective. A folded BoxCARS phasematching geometry, on the other hand, results in an almost cylindrical interaction volume - at the cost of a reduced resolution, for which the possible vignetting of the CARS emission is much reduced. In addition, this type of phasematching provides spatial separation of the signal from the input laser beams, permitting simple signal detection of low frequency vibrational modes. Calculations show that when CARS is performed in a microscopic volume, the phasematching restraint on tuning over the vibrational band is strongly relaxed. A first example of CARS imaging using a folded BoxCARS imaging geometry is shown.

Journal Article↗

Blunt trauma to the spleen.

BACKGROUND: The management of splenic injury resulting from blunt trauma in adults is controversial, with an increasing trend towards non-operative management and conservation of the spleen. A retrospective review was performed on adult patients treated in a single institution for splenic injury resulting from blunt trauma in an attempt to identify factors important in selecting an appropriate management option and predicting the success of that option. METHODS: Associated injuries (standardized using Injury Severity Scores), clinical signs at presentation, computed tomographic grading of splenic injury, and transfusion requirements were documented. Statistical analysis was performed using non-parametric Mann-Whitney, Chi-squared, Kolmogorov-Smirnov and multivariate logistic regression tests. RESULTS: Eighty-five patients were identified. Non-operative management was used on 39 patients, splenic conservation on 14 patients, and splenectomy on 32 patients. The mean Injury Severity Score was significantly lower in the non-operative group. Computed tomographic grading of the splenic injury was not found to correlate well with intraoperative findings. Transfusion requirements were lower in the non-operative group. Non-operative management failed in four patients; two had continued splenic bleeding, and two required surgery for other intra-abdominal injuries. Overall mortality was 7%. There was one death in the splenic conservation group, unrelated to the splenic injury, and two patients required a second laparotomy and splenectomy for persistent splenic bleeding. There were five deaths in the splenectomy group, only one of which was related to the splenic surgery. CONCLUSION: Management of blunt splenic injury remains controversial. The decision to pursue non-operative management rather than splenic conservation or splenectomy depends on the individual merits of each case. There is an increasing trend towards splenic conservation, particularly in younger, stable patients with single organ injury.

Abdominal Injuries↗

Topological effects in ring polymers. II. Influence Of persistence length

The interplay of topological constraints and the persistence length of ring polymers in their own melt is investigated by means of dynamical Monte Carlo simulations of a three-dimensional lattice model. We ask if the results are consistent with an asymptotically regime where the rings behave like (compact) lattice animals in a self-consistent network of topological constraints imposed by neighboring rings. Tuning the persistence length provides an efficient route to increase the ring overlap required for this mean-field picture to hold: The effective Flory exponent for the ring size decreases down to nu less, similar1/3 with increasing persistence length. Evidence is provided for the emergence of one additional characteristic length scale d(t) approximately N0, only weakly dependent on the persistence length and much larger than the excluded volume screening length xi. At distances larger than d(t) the conformational properties of the rings are governed by the topological interactions; at smaller distances rings and their linear chain counterparts become similar. (At distances smaller than xi both architectures are identical.) However, the crossover between both limits is intricate and broad, as a detailed discussion of the local fractal dimension (e.g., obtained from the static structure factor) reveals. This is due to various crossover effects which we are unable to separate even for the largest ring size (N=1024) presented here. The increased topological interactions also influence the dynamical properties. Mean-square displacements and their distributions depend crucially on the ring overlap, and show evidence of the existence of additional size and time scales. The diffusion constant of the rings goes down from effectively D(N) approximately N-1.22 for flexible rings with low overlap to D(N) approximately N-1.68 for strongly overlapping semiflexible rings.

Journal Article↗

Collective modes in an open microwave billiard

Numerical calculations for a microwave Sinai billiard coupled strongly to a lead are performed as a function of the coupling strength between billiard and lead. They prove the formation of different time scales in an open quantum system at large coupling strength. The short-lived collective states are formed together with many long-lived trapped states.

Journal Article↗

Symmetric polymer blend confined into a film with antisymmetric surfaces: interplay between wetting behavior and the phase diagram

We study the phase behavior of a symmetric binary polymer blend that is confined in a thin film. The film surfaces interact with the monomers via short-range potentials. We calculate the phase behavior within the self-consistent field theory of Gaussian chains. Over a wide range of parameters we find strong first-order wetting transitions for the semi-infinite system, and the interplay between the wetting/prewetting behavior and the phase diagram in confined geometry is investigated. Antisymmetric boundaries, where one surface attracts the A component with the same strength as the opposite surface attracts the B component, are applied. The phase transition does not occur close to the bulk critical temperature but in the vicinity of the wetting transition. For very thin films or weak surface fields one finds a single critical point at straight phi(c)=1 / 2. For thicker films or stronger surface fields the phase diagram exhibits two critical points and two concomitant coexistence regions. Only below a triple point there is a single two-phase coexistence region. When we increase the film thickness the two coexistence regions become the prewetting lines of the semi-infinite system, while the triple temperature converges toward the wetting transition temperature from above. The behavior close to the tricritical point, which separates phase diagrams with one and two critical points, is studied in the framework of a Ginzburg-Landau ansatz. Two-dimensional profiles of the interface between the laterally coexisting phases are calculated, and the interfacial and line tensions analyzed. The effect of fluctuations and corrections to the self-consistent field theory are discussed.

Journal Article↗

Self-exciting chaos as a dynamic model for irregular neural spiking

We introduce a nonlinear dynamical system with self-exciting chaotic dynamics. Its interspike interval return map shows a noisy Poisson-like distribution. Spike sequences from different initial conditions are unrelated but possess the same mean frequency. In the presence of noisy perturbations, sequences started from different initial conditions synchronize. The features of the model are compared with experimental results for irregular spike sequences in neurons. Self-exciting chaos offers a mechanism for temporal coding of complex input signals.

Journal Article↗

Far upstream sequences regulate the human prolactin promoter transcription.

The human prolactin gene is mainly expressed in pituitary lactotrope cells, but transcription from an alternative, far upstream promoter was detected in lymphoid, placental and mammary cells. We describe the transcriptional activity in rat pituitary cells of the complete region separating the two promoters, using transient transfection experiments. A far upstream activating region was only functional in combination with the prolactin promoter. DNaseI protection experiments revealed, in addition to binding sites for the pituitary-specific factor Pit-1, sites (e.g. SD1) for several ubiquitous factors and one lymphoid-specific factor (SD4). A single copy of the ubiquitous site SD1 or the lymphoid-specific site SD4 was unable to activate transcription of a heterologous promoter in pituitary cells. However, SD1 activated transcription in nonpituitary cells and SD4 was functional specifically in lymphoid cells. Five copies of a distal site (D8) activated transcription in each cell type tested. Gel retardation experiments show that this site binds the specific factor C/EBP in liver and a distinct factor in other cell types. Our results suggest that different elements within this large region direct specific expression from each promoter via a complex interplay between cell-specific and ubiquitous transcription factors.

Amino Acid Sequence↗

Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.

PURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.

Adult↗

Silencing subdomains of v-ErbA interact cooperatively with corepressors: involvement of helices 5/6.

Members of the thyroid hormone receptor (TR) family act on vertebrate development and homeostasis by activating or repressing transcription of specific target genes in a ligand-dependent way. Repression by TR in the absence of ligand is mediated by an active silencing mechanism. The oncogene v-ErbA is a variant form of TR unable to bind hormone and thus acts as a constitutive repressor. Functional studies and mutation analysis revealed that the TR/v-ErbA silencing domain is composed of three silencing subdomains (SSD1-3) which, although nonfunctional individually, synergize such that silencing activity is restored when they are combined in a heteromeric complex. Here we demonstrate, using protein interaction assays in vitro and in vivo, that the inactive v-ErbA point mutant L489R within helix 5/6 in SSD2 fails to interact with the two corepressors N-CoR (nuclear receptor corepressor) or SMRT (silencing mediator of retinoic acid and thyroid hormone receptor). Furthermore, mutants in SSD1 and SSD3 exhibit a reduced corepressor recruitment corresponding to their weak residual silencing activity. In mammalian two-hybrid assays, only the combination of all three silencing subdomains, SSD1-3, leads to a cooperative binding to the corepressors N-CoR or SMRT comparable to that of the full-length v-ErbA repression domain. In conclusion, full silencing activity requires corepressor interaction with all three silencing subdomains, SSD1-3. Among these, SSD2 is a new target for N-CoR and SMRT and is essential for corepressor binding and function.

Animals↗

The composition of old age homes in South Africa in relation to the residents and nursing personnel.

This research project is the first phase of a larger study aimed at describing and exploring the cost-effective utilisation of nursing personnel in old age homes in South Africa. The aim in the first phase was to describe the composition of the residents and nursing personnel of old age homes in South Africa. An exploratory and descriptive survey was conducted and the data was collected by means of a questionnaire. The questionnaire also included data on the financial implications of utilising professional nursing personnel to manage the care of the frail residents/older persons in old age homes in South Africa. The questionnaires were mailed to 612 old age homes published in the Hospital and Nursing Yearbook of 1997 (100% sample). A total of 145 (23.69%) questionnaires were returned and included in the descriptive data analysis. The residents are mainly female (77%), older than 85 years of age, belong to the white race group (83.74%) and are highly dependent on nursing care and supervision (69.7%). Old age homes are mainly managed/controlled by welfare organisations and lay health care workers are utilised to a large extent (42.22% of the nursing workforce) to render nursing care to the frail residents. The cost-effective utilisation of nursing personnel (registered and enrolled), as well as the utilisation of lay health workers in old age homes, needs to be critically examined.

Age Distribution↗

[Isolated sphenoiditis treated with endoscopic surgery in a child].

Isolated sphenoiditis in childhood is a rare entity which is often very difficult to diagnose with conventional techniques. The authors present a case of sphenoiditis in nine years old boy, where chronic rhinitis and persistent cephalqia where the main symptoms. The diagnosis was made on the base of computed tomography and nasal endoscopy. Because of lack of effect after pharmacological treatment the child was submitted to endoscopic surgery--sphenoethmoidectomy, which resulted it total recovery. The diagnosis, indications to computed tomography of paranasal sinuses in children, options of both conservative and surgical treatment and possible complications of the diseases are discussed.

Child↗

The effectiveness of osteopathic manipulative treatment as complementary therapy following surgery: a prospective, match-controlled outcome study.

CONTEXT: Osteopathic manipulative treatment has been reported to relieve a variety of conditions, but no studies have examined the outcome effects of osteopathic manipulative treatment as a complementary modality for treating musculoskeletal problems during postoperative recovery. OBJECTIVE: To assess osteopathic manipulative treatment as a complementary therapy for patients undergoing elective knee or hip arthroplasty. DESIGN: Prospective, single-blinded, 2-group, match-controlled outcome study. SETTING: Osteopathic teaching hospital. PATIENTS: Of 166 eligible patients, 38 were assigned to a treatment group and matched with 38 control subjects. INTERVENTION: The treatment group received osteopathic manipulative treatment on postoperative days 2 through 5. MAIN OUTCOME MEASURES: Days to independent negotiation of stairs, distance ambulated, supplemental intramuscular analgesic use, length of hospital stay, and patients' perceptions of treatment. RESULTS: Compared to control subjects, the intervention group negotiated stairs 20% earlier (mean = 4.3 postoperative days, SD = 1.2; control subjects 5.4, SD = 1.6, P = .006) and ambulated 43% farther on the third postoperative day (mean = 24.3 m, SD = 18.3; controls = 13.9, SD = 14.4, P = .008). The intervention group also required less analgesia, had shorter hospital stays, and ambulated farther on postoperative days 1, 2, and 4. CONCLUSIONS: Patients receiving osteopathic manipulative treatment in the early postoperative period negotiated stairs earlier and ambulated greater distances than did control group patients.

Aged↗