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Biomedical subjects

K Ludwig

Publications and source records attributed to K Ludwig.

At least 19 recordsLinked to original sources

Mathematical simulation of retinal image contrast after photorefractive keratectomy with a diaphragm mask.

BACKGROUND: Photorefractive keratectomy (PRK) using a dilating diaphragm mask engraves a delicate three-dimensional staircase pattern into a formerly smooth corneal surface. The created steps are later smoothed by tear film and wound healing processes. The present study investigates, in a mathematical simulation, the effects that such staircase patterns and their smoothing may have on retinal image contrast. METHODS: All simulations are based on the Gullstrand eye model and calculate retinal image contrast from point spread function (PSF) analysis of Gullstrand eyes treated by simulated PRK under various conditions. RESULTS: The simulations indicate that PRK can reduce retinal contrast markedly. The most critical factor for such a reduction is the step height of the ablation pattern. With step heights below 0.4 microns, loss of contrast due to the created staircase pattern is always moderate and should be restored during early wound healing. Complete wound healing may smooth out larger step heights. Micromovements during PRK also can lead to partial loss of retinal image contrast. CONCLUSIONS: Simulation of retinal contrast after PRK shows that step heights below 0.4 microns seem to be acceptable. A minimization of the micromovements during PRK can offset some of the reduction of retinal contrast.

Contrast Sensitivity

[Decrease of retinal image contrast after photorefractive keratectomy, improvement within the scope of surface restitution].

Photorefractive keratectomy (PRK) with the ArF excimer lasers in current use usually approximates the intended corneal curvature by a mean of a delicate step-type pattern that is smooth off afterwards by reepithelialization and tear film. The present study was based on a model eye with axial myopia of -6 D but otherwise the optical and geometric properties of the Gullstrand model eye and was designed to investigate to what extent. (1) corneal step patterns can reduce retinal image contrast and (2) smoothing effects can restore such a loss. METHODS. The corneal surface resulting from PRK in the case of a myopia of -6 D (optical zone diameter 6 mm) is calculated for the parameters of the model eye. The retinal image contrasts of bar patterns are calculated by PSF (point spread function) analysis: varying size of pupil, wavelength, bar width, ablation step height and degree of smoothing. RESULTS. Step height influences retinal image contrast crucially. With step heights above 0.4 micron a massive loss of retinal image contrast must be expected, which can, however, be corrected to a useful extent by surface-smoothing effects. CONCLUSION. This study indicates that PRK with excimer lasers should be performed with low fluence and correspondingly low corneal step heights.

Computer Simulation

[Reactive oxygen species in the pathogenesis of gastrointestinal tumors. A follow-up study].

UNLABELLED: Development and growth of gastrointestinal tumors seems to correlate closely with the formation of reactive oxygen intermediates (ROI). It is known, that oxygen-free-radicals are able to induce a precancerous stage and tumor growth by damaging DNA or changing the protein and lipid structure. To investigate, whether the cellular formation of oxygen-free radicals plays a role in the pathogenesis of colorectal carcinoma, we performed the study presented here. 40 patients with colorectal carcinoma were studied over a period of 6 months (before operation, 10 days after operation, 3 months later, 6 months later). Oxygen-free radicals were determined by chemiluminescence response in the whole blood, in granulocytes and in monocuclear blood cells (MBC). At the same time the trace elements selenium, Copper and Zinc, known to play an important role as antioxidants, were measured. RESULTS: We observed, that the ability of granulocytes for phagocytosis was depleted. However, this effect could be reversed as demonstrated in in vitro stimulation assays. After 6 months the phagocytosis by granulocytes achieved again normal values. Simultaneously a dramatic increase in superoxide-anions generated by mononuclear blood cells was seen. This increase was still obvious after 6 month. Independent of the tumor state selenium deficiency was found in all patients. Since no substitution of selenium was performed after operation, this deficiency was not normalised. CONCLUSION: The ability for phagocytosis and therefore the immune response is reduced in a reversible manner. In addition reactive superoxide-anions, that are able to induce tumors, are formed. This risk is increased in the absence of selenium. Thus, clinical follow-up studies are needed to determine subclinical tumor relapses and to investigate the role of oxidative stress by chemi-luminescence. As consequence of this study selenium substitution seems to be indicated.

Aged

Analysis of delay times of hemagglutinin-mediated fusion between influenza virus and cell membranes.

We have studied the kinetics of low pH-induced fusion between influenza virus A/PR 8/34 and human erythrocyte membranes in suspension by using an assay based on fluorescence dequenching (FDQ) of the lipophilic dye octadecylrhodamine B chloride (R 18). As shown previously (Clague et al. 1991) the onset of FDQ is preceded by a characteristic lag time (tlag) following pH reduction. Whereas tlag represents only a subpopulation of fusing viruses with the shortest delay time we suggest here that a representative mean lag time mu lag of virus-cell fusion can be deduced from the R 18-assay. Kinetics of FDQ reflects the cumulative distribution function of lag times tau lag of single fusion events with the mean value mu lag. We show that tau lag obtained from the onset of FDQ does not always reflect the fusion behaviour of the whole population of fusing viruses. While both lag times, taulag and mu lag, exhibit a similar temperature dependence we found a significantly different dependence of both delay times on virus inactivation by low pH-pretreatment. We conclude that the mean lag time mu lag appears to be a more appropriate parameter describing the kinetics of virus-cell fusion. The analysis of delay times offers a new approach to test the validity of different kinetic models of HA-mediated fusion and to gain valuable information about HA-mediated fusion. The analysis confirms that the inactivation process proceeds via steps of the formation of the fusion pore. Although the increase of lag times can be explained by a depletion of fusion competent HA's, our data suggest that intermediate structures of HA along the inactivation pathway can still transform into a fusion site.

Cells, Cultured

Human colonic smooth muscle electrical activity during and after recovery from postoperative ileus.

Colon smooth muscle electrical control (ECA) and response activities (ERA) were recorded for up to 4 wk postoperatively for 48 patients after major abdominal operations. Bipolar electrodes were implanted into right and left colon circular muscle and exteriorized through the flanks, and signals were tape recorded for 2-24 h daily beginning on the 1st postoperative day. A computer program was used for data reduction and analysis. Recorded signals were digitized and filtered. The ECA frequency components were identified by fast Fourier transformation, and their relative tenancy in low, mid, and high frequency ranges was determined. Short and long ERA burst duration and frequency and number and velocity of propagating long ERA bursts were determined. ECA was omnipresent and exhibited a downshift of the dominant frequency from the mid to the low range as recovery from postoperative ileus progressed. Concurrently, first in the right and then in the left colon, the frequency of long ERA bursts increased, followed by the appearance of propagating long ERA. After the 6th postoperative day, no further significant changes in parameters of colon electrical activity occurred with time.

Adolescent

Microsatellite-based fine mapping of the Van der Woude syndrome locus to an interval of 4.1 cM between D1S245 and D1S414.

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder characterized by lip pits, clefting of the primary or secondary palate, and hypodontia. The gene has been localized, by RFLP-based linkage studies, to region 1q32-41 between D1S65-REN and D1S65-TGFB2. In this study we report the linkage analysis of 15 VWS families, using 18 microsatellite markers. Multipoint linkage analysis places the gene, with significant odds of 2,344:1, in a 4.1-cM interval flanked by D1S245 and D1S414. Two-point linkage analysis demonstrates close linkage of VWS with D1S205 (lod score [Z] = 24.41 at theta = .00) and with D1S491 (Z = 21.23 at theta = .00). The results revise the previous assignment of the VWS locus and show in an integrated map of the region 1q32-42 that the VWS gene resides more distally than previously suggested. When information about heterozygosity of the closely linked marker D1S491 in the affected members of the VWS family with a microdeletion is taken into account, the VWS critical region can be further narrowed, to the 3.6-cM interval between D1S491 and D1S414.

Abnormalities, Multiple

[Photocoagulation in the edematous and non-edematous retina with the cw-laser of different wavelengths].

The impact of wavelength upon the laser power required in photocoagulation of oedematous and non-oedematous retinal areas was investigated in a restricted clinical study. The following laser systems were applied: an argon laser (514 nm), a diode-pumped frequency-doubled Nd:YAG laser (532 nm) and a diode laser (810 nm). All lasers had broadly similar properties as regards beam characteristics, beam conduction and application optics. Twenty-five eyes of 25 patients with diabetic retinopathy were included in the study. Each eye was treated with each laser in areas of edema and no edema. Apart from the wavelength, laser power was the only variable permitted. The power required for photocoagulation at 514 nm and 532 nm was identical under every aspect of the study. In comparison with 514 nm or 532 nm photocoagulations, 810 nm photocoagulations required 6.0 +/- 0.9-fold higher power settings in nonedematous retina and 5.75 +/- 1.0 fold higher power settings in edematous retina. At every wavelength investigated, retinal edema raised the average laser power needed by more than 20%. The extent of this effect seems to decline with longer wavelengths.

Adult

The role of Escherichia coli O 157 infections in the classical (enteropathic) haemolytic uraemic syndrome: results of a Central European, multicentre study.

To assess the importance of infection by Verotoxin (VT) producing Escherichia coli (VTEC) in children with HUS in Central Europe, stool and/or serum samples obtained from 147 patients from 28 paediatric centres were prospectively examined for the presence of VTEC and the kinetics of faecal VT titres (FVT), and for VT neutralization titres and antibodies against E. coli O 157 lipopolysaccharide, respectively. Ninety-two percent of the patients had classic (enteropathic) HUS (E+ HUS). Evidence of VTEC infection was obtained in 86% of them. VTEC/FVT were identified in 55/118 E+ cases (47%). A prominent feature was the frequent isolation of sorbitol-fermenting, VT2-producing E. coli O 157.H-.VT1 (C600/H19) was neutralized by 9%, and VT2 (C600/933W) by 99% of the initial serum samples from E+ patients, compared to 3% (VT1) and 100% (VT2) from age-related controls. Fourfold titre rises against VT1 and/or VT2 were observed in 13/70 (19%), and significantly elevated O 157 LPS IgM and/or IgA antibodies in 106/128 (83%) of the E+ patients. The ubiquitous VT2 neutralizing principle in the serum of HUS patients as of healthy controls warrants further investigations.

Adolescent

The relationship between the physicochemical properties and the biological effects of alloxan and several N-alkyl substituted alloxan derivatives.

Alloxan causes diabetes in experimental animals through its ability to destroy the insulin-secreting B-cells of the pancreas. Alloxan is hydrophilic and chemically unstable; it is reactive toward thiols, undergoing redox cycling in the presence of glutathione and oxidizing protein-bound thiol groups, as reflected by inhibition of the thiol enzymes, hexokinase and glucokinase. It is apparently also selectively taken up by the GLUT-2 glucose transporter in the pancreatic B-cell membrane. In order to investigate which, if any, of these physicochemical properties are important in the toxic action of alloxan, we have examined seven N-alkyl substituted alloxan derivatives of various diabetogenic activity. Hydrophilicity was identified as a factor essential for diabetogenicity. Stability, rate of redox cycling and reactivity toward thiol groups were not correlated with diabetogenicity. Selective uptake by the GLUT-2 glucose transporter is not a prerequisite for the diabetogenicity of alloxan derivatives.

Alloxan

Photodynamic laser therapy of basal-cell carcinoma of the lid.

Photodynamic therapy (PDT) remains an experimental approach for the treatment of small, mainly superficial malignant tumors. When given intravenously, hematoporphyrin derivative (HpD) selectively photosensitizes tumor tissue. Activated by light of 630 nm wave-length, HpD leads to tumor necrosis. This paper presents the results of PDT to eyelid basal-cell carcinomas in 21 patients. All lesions primarily responded to the treatment and became necrotic. A generalized photosensitization lasting for more than 4 weeks was seen in all patients. In five patients, lid malformations due to scar formation were noted, being marked in three cases. Ten patients showed a recurrence of tumor after 3-12 months. At present, PDT has no advantage over well-established therapies for basal-cell carcinomas of the eyelid.

Aged

ph-dependent hydrophobicity profile of hemagglutinin of influenza virus and its possible relevance in virus fusion.

The hydropathy profile of hemagglutinin (HA) subunits HA1 and HA2 of influenza virus X31 and A/PR 8/34 is analyzed at different pH. At neutral pH (7.4) pronounced hydrophobic sequences of HA correspond to the N-terminus and the transmembrane spanning sequence of HA2. At pH 5.0 where influenza virus is known to fuse with biological membranes several hydrophobic sequences in the ectodomain exist which are comparable in both the hydrophobicity and length of the N-terminus of HA2. It is suggested that these hydrophobic stretches are important for the fusion complex, in addition to the N-terminal site of HA2.

Hemagglutinins

High incidence of serum antibodies to Escherichia coli O157 lipopolysaccharide in children with hemolytic-uremic syndrome.

Because the classic hemolytic-uremic syndrome has been etiologically linked to intestinal infections by Escherichia coli O157 and other verotoxin-producing E. coli (VTEC), we examined 22 consecutive children with acute hemolytic-uremic syndrome for the presence of VTEC, using microbiologic methods, and for a specific immune response to O157 lipopolysaccharide in acute-phase and follow-up sera, using the indirect hemagglutination assay and the immunoblot procedure. Of 22 children with enteropathic hemolytic-uremic syndrome, 15 (68%) had evidence of VTEC infection by culture of the pathogen or detection of free verotoxin in the feces, or both. Significantly elevated titers of short-lived agglutinins and IgM class antibodies against the O157 lipopolysaccharide were found in 20 (91%) of 22 patients, but not in two of three patients with non-O157 E. coli isolates or in healthy children or children with diarrhea caused by other enteric pathogens (p less than 0.01). The combined microbiologic and serologic procedures provided evidence for VTEC infection in all 22 patients. The high incidence of anti-O157 lipopolysaccharide antibodies in these patients indicates the predominance and the pathogenic potential of this serogroup. Both serologic techniques proved to be valuable tools to further characterize this form of hemolytic-uremic syndrome. Future studies on the induction of protective immunity seem warranted.

Antibodies, Anti-Idiotypic