Topical imiquimod eradicates skin metastases of malignant melanoma but fails to prevent rapid lymphogenous metastatic spread.
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Biomedical subjects
Publications and source records attributed to A Wagner.
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This study aims to provide a quantitative analysis of the factors affecting the actual precision and stability of optoelectronic and electromagnetic tracking systems in computer-aided surgery under real clinical/intraoperative conditions. A "phantom-skull" with five precisely determined reference distances between marker spheres is used for all measurements. Three optoelectronic and one electromagnetic tracking systems are included in this study. The experimental design is divided into three parts: (1) evaluation of serial- and multislice-CT (computed tomography) images of the phantom-skull for the precision of distance measurements by means of navigation software without a digitizer, (2) digitizer measurements under realistic intraoperative conditions with the factors OR-lamp (radiating into the field of view of the digitizer) or/and "handling with ferromagnetic surgical instruments" (in the field of view of the digitizer) and (3) "point-measurements" to analyze the influence of changes in the angle of inclination of the stylus axis. Deviations between reference distances and measured values are statistically investigated by means of analysis of variance. Computerized measurements of distances based on serial-CT data were more precise than based on multislice-CT data. All tracking systems included in this study proved to be considerably less precise under realistic OR conditions when compared to the technical specifications in the manuals of the systems. Changes in the angle of inclination of the stylus axis resulted in deviations of up to 3.40 mm (mean deviations for all systems ranging from 0.49 to 1.42 mm, variances ranging from 0.09 to 1.44 mm), indicating a strong need for improvements of stylus design. The electromagnetic tracking system investigated in this study was not significantly affected by small ferromagnetic surgical instruments.
STUDY OBJECTIVE: Prospective studies have shown a consistent relation between alcohol consumption and decreasing incidence of coronary artery disease. The protective effect of alcohol could be mediated through increased levels of HDL cholesterol (HDL-c). The aim of this study was to examine the relation between blood lipid levels and the consumption of different types of alcoholic beverages among 1581 men and 1535 women. DESIGN: Data from representative cross sectional surveys (1994-1997) in three different regions of France were used. The consumption of the different types of alcohol was quantified using a recall method according to a typical weekly consumption. MAIN RESULTS: The median daily alcohol intake was 24 g for men and 4 g for women. After adjustment for confounders, total alcohol showed a positive and significant association with HDL-c and triglycerides (TG) in both sexes. In multivariate analysis, wine was positively associated with HDL-c. Beer was positively associated with HDL-c in men and with triglycerides in men and women. When taking drinking patterns into account, wine drinkers had higher HDL-c levels than non-wine drinkers. Differences became non-significant after adjustment for confounders and particularly for socioeconomic parameters. CONCLUSIONS: In a French population sample, total alcohol was positively associated with HDL-c and triglycerides. The specific influence of any particular alcoholic beverage on blood lipids was not clearly demonstrated but wine preference found in a group with higher lifestyle standards was associated with a more favourable blood lipid profile.
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New data are presented on the p(e,e'p)pi(0) reaction at threshold at a four-momentum transfer of Q(2) = 0.05 GeV(2)/c(2). The data were taken with the three-spectrometer setup of the A1 Collaboration at the Mainz Microtron MAMI. The complete center of mass solid angle was covered up to a center of mass energy of 4 MeV above threshold. Combined with measurements at three different values of the virtual photon polarization epsilon, the structure functions sigma(T), sigma(L), sigma(TT), and sigma(TL) are determined. The results are compared with calculations in heavy baryon chiral perturbation theory and with a phenomenological model. The measured cross section is significantly smaller than both predictions.
BACKGROUND AND OBJECTIVE: Patients with diabetic foot infection (DFI) have a high rate of infection, up to 40%, with methicillin-resistant Staph. aureus (MRSA). Having noticed a definite increase of such patients in our special unit, we initiated a drastic change of hygienic measures and here report the results. PATIENTS AND METHODS: 788 patients with DFI (mean age 67.3 [32-90] years, 62% males) were admitted between 1.1.1999 and 31.7.2000. Before 31.7.1999, the following hygienic measures had been in place: cohort isolation, protective closing, implementation of general hygienic rules. Since 1.8.1999, modified measures have been undertaken: primary single-patient isolation, concentration in one ward of all patients with MRSA, medical care only by trained personnel, admission of patients only after microbiological results were known or primary solitary isolation. Algorithms were used for the transmission of all necessary information. RESULTS: MRSA was demonstrated in 64 patients. The number of infections during the hospital stay, before and after the change of hygienic measures were 9 (27%) and 2 patients (8%), respectively. The sites of MRSA colonisation and proven eradication were: nasopharynx only, 3 with 67% eradication; MRSA in a wound, 25 with 28% eradication. In comparison to the yearly statistic on wound healing in DFI 1999 (n=613) the following results are shown (patients with MRSA in brackets): healing rate with conservative treatment 61.5% (20%), minor-amputation 30.5% (52%), major-amputation 4.5% (22%), death 3.5% (6%). CONCLUSIONS: The rate of new infections were dramatically reduced by changing the hygienic measures. The rate of successful sanitation was unsatisfactoy. Patients with MRSA showed markedly poorer treatment results in respect to wound healing.
HISTORY AND ADMISSION FINDINGS: A 86-year-old woman with chronic renal failure was treated with allopurinol for asymptomatic hyperuricemia. After one week she developed quickly progressive exanthema, bullous eruptions, epidermolysis, fever of 39.1; C and dyspnoea at rest. DIAGNOSIS, TREATMENT AND COURSE: The diagnosis of an allopurinol-induced hypersensitivity syndrome with toxic epidermal necrolysis was made from the history, the typical clinical picture and a skin biopsy. Initial therapy starts with steroids. Because of a lack of clinical improvement therapy was changed to immunoglobulins. In addition, systemic analgesia and cardiocirculatory supportive therapy were given. Because of increasing somnolence and severe pain intubation and controlled artificial ventilation were initiated. Despite intensive therapy progressive multi- organ failure developed and the patient died 3 weeks after start of symptoms. CONCLUSIONS: The life threatening hypersensitivity syndrome with fever, eosinophilia, hepatitis, renal failure and skin eruptions as severe as epidermal necrolysis is the most dangerous complication of therapy with allopurinol. The trigger seems to be oxipurinol, the main metabolite of allopurinol, which particularly accumulates in patients with renal failure and concomitant therapy with thiazides. There is no specific treatment of the disease. The use of allopurinol in patients with asymptomatic hyperuricaemia is not indicated in most cases. Dose adjustment according to the clearance of creatinine is mandatory.
The serum- and glucocorticoid-dependent kinase SGK1 is regulated by alterations of cell volume, whereby cell shrinkage increases and cell swelling decreases the transcription, expression and activity of SGK1. The kinase is expressed in all human tissues studied including the brain. The present study was performed to localize the sites of SGK1 transcription in the brain, to elucidate the influence of the hydration status on SGK1 transcription and to explore the functional significance of altered SGK1 expression. Northern blot analysis of human brain showed SGK1 to be expressed in all cerebral structures examined: amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus and thalamus. In situ hybridization and immunohistochemistry in the rat revealed increased expression of SGK1 in neurons of the hippocampal area CA3 after dehydration, compared with similar slices from brains of euvolaemic rats. Additionally, several oligodendrocytes, a few microglial cells, but no astrocytes, were positive for SGK1. The abundance of SGK1 mRNA in the temporal lobe, including hippocampus, was increased by dehydration and SGK1 transcription in neuroblastoma cells was stimulated by an increase of extracellular osmolarity. Co-expression studies in Xenopus laevis oocytes revealed that SGK1 markedly increased the activity of the neuronal K+ channel Kv1.3. As activation of K+ channels modifies excitation of neuronal cells, SGK1 may participate in the regulation of neuronal excitability.
Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 are responsible for the majority of hereditary nonpolyposis colorectal cancer (HNPCC) families. A common mutation mechanism is to disrupt MLH1 and MSH2 mRNA splicing. The disruption creates aberrant mRNAs lacking specific coding exons (exon skipping). Here, we report a novel skipping of MLH1 exon 12 caused by an AAG to TAG nonsense mutation at codon 461 in three HNPCC families of North American origins. The nonsense codon was found in a conserved haplotype in the three unrelated families and seems to represent a founder mutation. The skipping created an aberrant MLH1 mRNA transcript lacking exon 12. The effect of the codon 461 nonsense mutation on exon 12 skipping is evident even though it was placed in a minigene construct containing entirely different coding sequences. Notably, the effect of the nonsense mutation on exon skipping is incomplete. Accordingly, a second aberrant MLH1 transcript encompassing the nonsense codon is also produced. Whereas the latter transcript is unstable, presumably because of nonsense-mediated mRNA decay, neither of the aberrant transcripts seems to affect the stability of wild-type MLH1 mRNA. This study demonstrates that the germ-line nonsense mutation at codon 461 of MLH1 disrupts normal MLH1 mRNA processing, and that exon skipping underlies pathogenesis in these HNPCC families.
The metabolic network of the catabolic, energy and biosynthetic metabolism of Escherichia coli is a paradigmatic case for the large genetic and metabolic networks that functional genomics efforts are beginning to elucidate. To analyse the structure of previously unknown networks involving hundreds or thousands of components by simple visual inspection is impossible, and quantitative approaches are needed to analyse them. We have undertaken a graph theoretical analysis of the E. coli metabolic network and find that this network is a small-world graph, a type of graph distinct from both regular and random networks and observed in a variety of seemingly unrelated areas, such as friendship networks in sociology, the structure of electrical power grids, and the nervous system of Caenorhabditis elegans. Moreover, the connectivity of the metabolites follows a power law, another unusual but by no means rare statistical distribution. This provides an objective criterion for the centrality of the tricarboxylic acid cycle to metabolism. The small-world architecture may serve to minimize transition times between metabolic states, and contains evidence about the evolutionary history of metabolism.
INTRODUCTION: The aim of the study was to describe the clinical, radiological, and functional results of intramedullary nailing of deformities in the lower extremities of children with osteogenesis imperfecta after the use of multiple osteotomies and non-telescoping rods (rush pins). MATERIAL AND METHODS: Eight children with osteogenesis imperfecta, who consecutively underwent surgery during 1991-1994, were entered in the study. RESULTS: Sixteen operations were performed on eight children: 12 on the femur and four on the tibia. Like others, we found a high complication rate, 50%. Radiological correction of angular deformities was good. The functional outcome was satisfactory and the patients were satisfied. CONCLUSION: Correction and stabilisation of deformities in the lower extremities in children with osteogenesis imperfecta with the use of non-telescoping rods is an acceptable method of decreasing fractures and allowing most formerly non-ambulatory children to walk. Furthermore, the cosmetics were improved.
INTRODUCTION: Conventionally, cranionasal cerebrospinal fluid (CSF) fistulas have been closed by repair of the dural defect via an open craniotomy. These techniques may be cumbersome, not without complications, and far from successful. In recent years, endoscopic techniques have been developed in the field of nasal surgery and neurosurgery. Furthermore, by means of computer-aided surgery or neuronavigation, it is possible to identify the surgical track with a high degree of accuracy and, by the same token, identify the defect in the cranium. METHOD: By combining the endoscopic technique with computer-aided surgery, we have operated on six patients with cranionasal CSF fistulas endonasally. The fistula was confirmed before surgery by subaracnoidal injection of fluorescein. RESULTS: The surgery was successful and without any complications in all six cases. DISCUSSION: The method is recommended as the operation of first choice for cranionasal CFS fistulas, as compared to transcranial surgery. It is probably more efficient and with fewer complications than conventional surgery. A collaboration between neurosurgeons and ENT surgeons, like ours, can be recommended.
1. In human pennate muscle, changes in anatomical cross-sectional area (CSA) or volume caused by training or inactivity may not necessarily reflect the change in physiological CSA, and thereby in maximal contractile force, since a simultaneous change in muscle fibre pennation angle could also occur. 2. Eleven male subjects undertook 14 weeks of heavy-resistance strength training of the lower limb muscles. Before and after training anatomical CSA and volume of the human quadriceps femoris muscle were assessed by use of magnetic resonance imaging (MRI), muscle fibre pennation angle (theta(p)) was measured in the vastus lateralis (VL) by use of ultrasonography, and muscle fibre CSA (CSA(fibre)) was obtained by needle biopsy sampling in VL. 3. Anatomical muscle CSA and volume increased with training from 77.5 +/- 3.0 to 85.0 +/- 2.7 cm(2) and 1676 +/- 63 to 1841 +/- 57 cm(3), respectively (+/- S.E.M.). Furthermore, VL pennation angle increased from 8.0 +/- 0.4 to 10.7 +/- 0.6 deg and CSA(fibre) increased from 3754 +/- 271 to 4238 +/- 202 microm (2). Isometric quadriceps strength increased from 282.6 +/- 11.7 to 327.0 +/- 12.4 N m. 4. A positive relationship was observed between theta(p) and quadriceps volume prior to training (r = 0.622). Multifactor regression analysis revealed a stronger relationship when theta(p) and CSA(fibre) were combined (R = 0.728). Post-training increases in CSA(fibre) were related to the increase in quadriceps volume (r = 0.749). 5. Myosin heavy chain (MHC) isoform distribution (type I and II) remained unaltered with training. 6. VL muscle fibre pennation angle was observed to increase in response to resistance training. This allowed single muscle fibre CSA and maximal contractile strength to increase more (+16 %) than anatomical muscle CSA and volume (+10 %). 7. Collectively, the present data suggest that the morphology, architecture and contractile capacity of human pennate muscle are interrelated, in vivo. This interaction seems to include the specific adaptation responses evoked by intensive resistance training.
The development of a new and efficient synthesis of resin-bound N-(alpha-methoxyalkyl)amides is described. The condensation of aldehydes on a supported amide in the presence of trimethyl orthoformate afforded, in acidic media, the resin-bound N-acyliminium ion precursors. Repeating the reaction a second time led to a great improvement in yields, demonstrating one advantage of the solid-phase chemistry for the handling of sensitive intermediates difficult to isolate.
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