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Biomedical subjects

C Hartmann

Publications and source records attributed to C Hartmann.

At least 55 records · Page 3Linked to original sources

Whole-body cesium 137 activity up to 4 years after the Chernobyl reactor accident in premature newborns, newborns, infants, and children.

Cesium 137 activity was measured after the Chernobyl incident in a whole-body radiation counter (4-pi-scintillation counter) in 85 premature and mature newborns (group 1), 174 infants and young children up to 2 11/12 years (group 2), and 48 children between 3 and 8 years (group 3) from Bonn (Germany) and surroundings. In 1987 the mean level of radioactivity in group 2, at 3.7 Bq/kg body weight corresponding to a mean radiation exposure of 11 muSv/y, was lower than that of group 1 (5.8 Bq/kg, 17 muSv/y) and 3 (9.4 Bq/kg, 28 muSv/y). Up to 1990 the values of all groups revealed a continuous decrease. The latest measurements showed mean values of 0.5 Bq/kg (1.5 muSv/y) in group 1, 0.6 Bq/kg (1.8 muSv/y) in group 2, and 0.8 Bq/kg (2.4 muSv/y) in group 3. A comparison with present cesium 137 values and determinations of the end of the 1950s and beginning of 1960s, both in adults, showed good agreement. The effective dose-equivalent rates amounted to less than 1% of that from natural radiation exposure. These levels should present no teratogenic risks to the population studied and, while there are theoretical mutagenic risks, the dose is so low that no increase in measurable mutagenic effects should be observed.

Accidents

Structure-function studies of substrate oxidation by bovine serum amine oxidase: relationship to cofactor structure and mechanism.

The chemical mechanism of substrate oxidation, catalyzed by bovine serum amine oxidase, has been explored by a detailed investigation of structure-reactivity correlations. Past mechanistic studies, involving the reductive trapping of substrate to cofactor [Hartmann, C., & Klinman, J. P. (1987) J. Biol. Chem. 262, 962], implied the intermediacy of a substrate imine complex in the catalytic redox mechanism. These studies led to the proposal of a transamination mechanism for substrate oxidation, analogous to pyridoxal phosphate dependent enzymes. In pyridoxal phosphate catalyzed reactions, the transamination process involves the transient formation of a resonance-stabilized carbanion intermediate. Although evidence has been presented describing the participation of an active site base in bovine serum amine oxidase catalysis [Farnum, M. F., Palcic, M. M., & Klinman, J. P. (1986) Biochemistry 25, 1898], the nature of the intermediate derived from C-H bond cleavage has not been directly addressed. To examine this question, a structure-reactivity study was performed using a series of para-substituted benzylamines. Having prior knowledge of the intrinsic isotope effect for an enzymatic reaction permits calculation of microscopic rate constants from steady-state data [Palcic, M. M., & Klinman, J. P. (1983) Biochemistry 22, 5957]. Deuterium isotope effects on kcat and kcat/Km parameters were determined for all substrates, allowing for the calculation of rate constants for C-H bond cleavage (k3) and substrate dissociation constants (Kd). Pre-steady-state constants obtained for p-acetylbenzylamine, p-(trifluoromethyl)benzylamine, and unsubstituted benzylamine exhibited excellent agreement with values calculated from steady-state isotope effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)

A pharmacokinetic model describing the removal of circulating radiolabeled antibody by extracorporeal immunoadsorption.

Extracorporeal immunoadsorption is a new technique for removal of circulating radiolabeled antibody from the peripheral blood (1) to reduce background activity for improved tumor imaging, and (2) to reduce whole-body and marrow toxicity when high doses of radiolabeled antibodies are used for antitumor therapy. A pharmacokinetic model was developed to describe plasma disappearance of 111In-KC-4G3 prior to, during, and after immunoadsorption in humans. The model is developed based on a two-compartment open model, and during immunoadsorption a third compartment is added for removed radioactivity by the immunoadsorption column. Goodness-of-fit statistics indicate a good fit of the model to the data. The resulting pharmacokinetic parameters for a selected patient are V1 = 2.64 L, VSS = 3.64 L, t 1/2 alpha = 3.77 hr, and t 1/2 beta = 48.5 hr. The immunoadsorption clearance (CLIA = 19.3 ml/min) was 21-fold greater than the patient's plasma clearance (CL10 = 0.899 ml/min), indicating a very effective immunoadsorption process. The model predicts an increase in plasma radioactivity upon termination of immunoadsorption, probably due to redistribution of radioactivity from the extravascular compartment to the plasma in response to the rapid decline in plasma radioactivity during immunoadsorption. Two series of simulations were performed to examine the influence of onset time and duration of immunoadsorption. In series one the onset time was varied and in series two immunoadsorption duration was varied. In series one, the predicted radioactivity amounts adsorbed by the immunoadsorption column ranged from 75% of the injected dose (4-hr onset) to 52% of the injected dose (24-hr onset). In series two, immunoadsorbed radioactivity ranged from 32% (2-hr duration) to 64% of the injected dose (12-hr duration). When instituted as early as 4 hr, the predictions suggest that earlier immunoadsorption onset improves the effectiveness of radioactivity removal, relating to higher early circulation concentrations, and longer immunoadsorption periods remove more radioactivity, but also result in larger predicted radioactivity redistribution form tissue to plasma. To employ the immunoadsorption procedure for tumor imaging and therapy optimally, the data and our predictions indicate that a compromise must be made that will balance immunoadsorption onset and duration against tumor radioactivity uptake and subsequent radioactivity redistribution from tissues back to plasma. Together with biologic considerations providing sufficient antigen-antibody interaction and dependent on the utilized radioisotope, these data support the utility of extracorporeal immunoadsorption during the radioimmunodetection of cancer and for future therapeutic applications.

Adsorption

Late onset endophthalmitis associated with intraocular lens: a case of molecularly proved S. epidermidis aetiology.

A case of severe endophthalmitis after cataract extraction followed by posterior chamber lens implantation is reported. Microbiological cultures from a tap of the patient's aqueous humour prior to lens explantation as well as from the explanted lens and aqueous and vitreous humour during operation yielded Staphylococcus epidermidis sensu stricto. Scanning electron microscopy showed massive colonisation of the lens loop by staphylococci. Clonal identity of all isolates was demonstrated by plasmid DNA analysis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of extra-cellular products. This is strongly suggestive of the aetiological role of S. epidermidis in this case of late onset endophthalmitis.

Aged

[Damage to the corneal endothelium caused by radial keratotomy].

In our experimental study on 53 rabbits we compared the amount of corneal endothelial damage caused by radial keratotomy (RK) referred to (1) the number of incisions (4, 8, or 16), (2) the postoperative interval (0 h, 48 h) and (3) the direction of the incision [centripetal (cp), centrifugal (cf)]. The endothelial damage was quantified by means of the Janus green photometry technique. Morphological changes were evaluated by scanning electron microscopy (SEM). Depending on the group examined, we found endothelial damage extending over 3-7% of an analysed surface of 64 mm2. One perforation caused endothelial damage of up to 17% of the surface examined. Increasing the number of incisions from 4 to 8 or 16 resulted in a statistically significant increase in the amount of endothelial damage (4.2%, 5.1%, 5.8%; P less than 0.05). At 0 h it was significantly higher than after 48 h (5.5%, 4.6%; P less than 0.05). The direction of the incision had no statistically significant influence in our study (zp: 5.2%, zf: 4.9%). The morphological changes in the rabbit corneal endothelium examined directly after the RK procedure were ruptures in the cell membranes, loss of cells, and posterior corneal protrusions beneath the incisions. After 48 h, we found fewer damaged cells and no denuded Descemet's membranes, but larger polymorphy of the cells and a numerical increase in the microvilli of the cells surrounding the damaged cells. Our results support the crucial argument against RK: the alteration and destabilization of healthy corneal tissue up to the endothelium.

Animals

Biocompatibility of a refractive intracorneal PMMA ring.

Intrastromal ring (ISR) implantation is a promising concept in refractive corneal surgery. In theory, it has two main advantages: eccentric corneal surgery and reversibility after ISR explanation. We present our first experimental data on histobiocompatibility after implantation of a 0.2/1.0 mm vaulted polymethylmethacrylate (PMMA) ISR of 7.5 mm diameter with a specially designed "puzzle lock" using a suction-guided stromal channelling device. Ninety-six rabbit eyes were implanted and enucleated after a 24-h to 8-month follow-up to be period and processed for histology (n = 51), scanning electron microscopy (n = 30) and transmission electron microscopy (n = 9). In this study, the histological data are reported. Two main histopathological phases of stromal reaction were observed: (1) up to 3 months: mild inflammation, mostly mononuclear cell reaction with some macrophages; (2) over 3 months: moderate fibrosis surrounding the ISR filling irregularities of the stromal channel. Mild scarring and rare circumscribed vascularization occurred at the sutured peripheral insertion site of the ISR. Persistent epithelial atrophy without erosion or ulceration was regularly observed over the bulging shoulder of the ISR. There was no significant endothelial surgical trauma due to ISR placement. Major complications occurred in 11 cases (11.5%): stromal abscess starting from the incision (n = 8) and massive neovascularization (n = 3). However, the incidence of complications regressed with improved surgical technique. In conclusion, there is good middle-term tolerance of the PMMA ring with a transparent central cornea.

Animals

Reductive trapping of substrate to methylamine oxidase from Arthrobacter P1.

Methylamine oxidase (EC 1.4.3.6) from Arthrobacter P1 was inactivated by NaCNBH3 in the presence of [14C]benzylamine, leading to the incorporation of 1 mol of radiolabeled substrate/mol of enzyme subunit at complete inactivation. By contrast, no labeling of enzyme was observed using [3H]NaCNBH3 as reductant. These results are analogous to those previously reported for the eukaryotic enzyme, bovine serum plasma amine oxidase [(1987) J. Biol. Chem. 262, 962-965]. The observed pattern of labeling is consistent with the presence of dicarbonyl cofactor at the active site of methylamine oxidase. Further, these studies suggest that our reductive trapping technique, in which the pattern of radiolabeling of an enzyme is compared using C-14 substrate vs tritiated reductant, may serve as a general assay for covalently bound dicarbonyl structures.

Arthrobacter

An internal part of the chloroplast atpA gene sequence is present in the mitochondrial genome of Triticum aestivum: molecular organisation and evolutionary aspects.

An internal part of the chloroplast atpA gene has been identified in the mitochondrial DNA of Triticum aestivum. It is located near the 18S-5S ribosomal genes and partially contained within a repeated sequence. Comparison of the transferred sequence with the original ct sequence reveals several nucleotide changes and shows that neither 5' nor 3' ends are present in the mt genome. No transcript of this region could be detected by Northern analysis. This sequence is present in mitochondrial genomes of other tetraploid and diploid species of Triticum, also in the vicinity of the 18S-5S ribosomal genes, suggesting a unique transfer event. The date of this event is discussed.

Adenosine Triphosphatases

Comparative enantioselective pharmacokinetic studies of celiprolol in healthy volunteers and patients with impaired renal function.

The pharmacokinetics of the beta 1-selective adrenergic antagonist (R,S)-celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to 8 healthy volunteers and 8 patients with various degrees of impaired renal function. No significant difference was found between the two enantiomers in the control group or in the patients. In healthy volunteers an average of 9.8% of the dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in the urine. Renal impairment reduced the urinary excretion of both enantiomers to the same extent according to the severity of the uraemia, producing higher AUCs. Nevertheless, the terminal half-lives of the R- and S-enantiomers were not significantly different between the groups. Dosage reduction in patients with renal impairment does not seem to be necessary.

Administration, Oral

[Morphology of capsular sack retraction in relation to capsulotomy technique, lens design and sulcus-/saccus fixation].

Over a period of several months the dynamics and morphology of capsular retraction were analyzed with various capsulotomy techniques and IOL types implanted into the capsular bag or the sulcus. The techniques compared were peripheral and intermediate canopener capsulotomy, intermediate and small letter-box capsulotomy, intermediate and small capsulorrhexis with and without superior incisions. The posterior chamber IOLs implanted were one-piece and three-piece C-loop lenses and, in a limited pilot study, one-piece disk lenses. The authors' results indicate that capsular retraction and the stable position of the implant depend on the type, form, and size of the capsulotomy, the type of IOL and its fixation in the bag or sulcus. Any irregularity of the anterior capsule induces irregular capsular retraction with the risk of IOL decentration. Free-floating anterior capsular flaps may induce formation of iridocapsular synechiae. Contact between the anterior capsular rim and the posterior capsule results in capsulocapsular adhesions, capsular wrinkling, and capsular opacification of the contact zone. In order to avoid these capsulocapsular adhesions the diameter of the IOL optics should exceed that of the capsular opening in endocapsular implantation. However, peripheral capsulocapsular adhesions are necessary to stabilize IOL haptics, which for this reason must be of open design. Capsulocapsular adhesions may inhibit migration of lens epithelial cells in secondary capsular opacification. The ideal anterior capsulotomy technique seems to be the symmetrical, small, circular, continuous capsulorrhexis, if endocapsular implantation is desired. However, the technique is mainly designed for phacoemulsification, as a small capsulorrhexis inhibits nuclear expression in extracapsular cataract extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy

[Endothelial protection in surgical interventions and corneal donor tissue].

Perioperative iatrogenic lesions due to physico chemical trauma may worsen a primary endotheliopathy or lead to a secondary endotheliopathy with subsequent decompensation and corneal opacification. The incisions in anterior segment surgery induce permanent vertical cellular disparity, considering the peripheral endothelium in an area that may correspond to its germinative zone. Cells are lost by corneal folding, e.g., during nuclear expression or sutureinduced distortion. Floating nuclear particles and a high perfusion volume, e.g., during phacoemulsification or vitrectomy in aphakic eyes, create diffuse cellular necrosis. The same thing happens with chemically or osmotically inadequate perfusion media or extraocular solutions applied to the open eye during surgical interventions, e.g., to maintain mydriasis. Large areas of cell erosion are encountered after direct contact with instruments and PMMA. This has been one of the reasons for the development of new IOL materials like Poly-Hema or silicone that are less traumatizing for the endothelium. Long-lasting endothelial lesions result from direct contact with IOL haptics or mobile iris- or angle-supported lenses. The effect of a short post-operative rise in IOP on the endothelium is not clear. For all lens styles and materials, it still remains unclear whether there is chronic subclinical inflammation due to the IOL plastic material itself or not. To protect the endothelium, e.g., during cataract surgery, several techniques have been developed: preoperative hypotony; nuclear expression respecting corneal topography; the use of small amounts of mostly physiological rinsing solutions warmed to body temperature; endocapsular irrigation-aspiration; posterior chamber phacoemulsification; posterior chamber IOL implantation with an anterior chamber deepened by air and/or viscoelastics; postoperative reduction of the IOP.(ABSTRACT TRUNCATED AT 250 WORDS)

Cataract Extraction

Changes in the electric resistance of the vaginal mucus in oestrous sows.

Changes in the electric resistance of the vaginal mucus were monitored in a large pig herd at 4-h intervals with a heat detector (Hauptner, Federal Republic of Germany) in multiparous sows (n = 16; litter size = 11.4 +/- 2.9) that showed a positive standing test and conceived. The initial value of resistance was 74.4 +/- 7.4 ohms. In 36 h this value gradually increased to 93.6 +/- 7.6 ohms. One to 2 h after the artificial inseminations (AI) lower resistance values were obtained, though the difference was not statistically significant. In the second part of the experiment 73.9% and 82.7% of the gilts (n = 92) and multiparous sows (n = 98) conceived, respectively, with an average litter size of 9.6 +/- 2.2 and 11.0 +/- 2.7, respectively. The conception rate of animals that immediately before AI had vaginal mucus resistance values between 75 and 90 ohms was about 20% higher. The only exception were 8 multiparous sows which had an average vaginal mucus resistance of 70 +/- 4.6 ohms after the first insemination. Litter size was also the biggest in sows with vaginal mucus resistance between 75 and 90 ohms. This difference was statistically significant for the multiparous sows. The heat detector is considered to be a useful complement to conventional methods of oestrus detection.

Animals

Simultaneous determination of (R)- and (S)-celiprolol in human plasma and urine: high-performance liquid chromatographic assay on a chiral stationary phase with fluorimetric detection.

The quantitative enantiospecific determination of the beta 1-selective adrenergic antagonist (R,S)-celiprolol in human plasma and urine is described. It involves a two-step liquid-liquid extraction of celiprolol from biological material and separation of the underivatized enantiomers by high-performance liquid chromatography on a chiral stationary phase (cellulose tris-3,5-dimethylphenyl carbamate, coated on silica gel) with fluorimetric detection. R-(+)-Propranolol was used as an internal standard. The detection limits of 1.5 ng/ml enantiomer in plasma and 2.5 ng/ml enantiomer in urine at signal-to-noise ratios higher than 3 permit the performance of pharmacokinetic studies after therapeutic doses.

Adrenergic beta-Antagonists

A new test for endothelial viability. The Janus green photometry technique.

A new in vitro technique was developed to measure, by simple photometry, the amount of Janus green extracted with absolute alcohol from isolated corneas after vital staining. The amount of stain corresponded to the percentage of damaged endothelial cells and was a reliable parameter of endothelial viability. More rapid and easier to perform than the usual cell counting of devitalized cells, this technique can be used to study the endothelial damage induced, for example, by experimental surgery, intraocular solutions, intraocular lens material, corneas storage solutions. As an example of application, results of the endothelial status after medium-term preservation of pig corneas (n = 40) in a modified McCarey-Kaufman medium at 4 degrees C were determined. The mean +/- endothelial damage was 8.5% +/- 1.8% (mean +/- SD) after 4 days, 29.5% +/- 3.7% after 7 days, 45.5% +/- 5.5% after 10 days, 69.3% +/- 3.7% after 14 days, and 100% after 20 days of storage in McCarey-Kaufman medium.

Animals

[Endothelial precipitates and cytomegalovirus infection].

In patients with the typical features of intraocular cytomegalovirus infection endothelial precipitates were identified that had a characteristic morphology, which included subtle, non-pigmented linear deposits with reticular arrangement that can spread diffusely over the corneal endothelium without preference for the inferior quadrants. The appearance of these precipitates was comparable to heterocromic cyclitis. Specular microscopy identified lymphocytes and macrophages on the endothelial layer. The present observations are based on five case reports of necrotizing retinitis, typical for intraocular cytomegalovirus infection, in connection with the atypical endothelial precipitates. In four of the five patients reported, HIV-infection was confirmed. In one patient with serologically confirmed cytomegalovirus infection (however without HIV-infection), a diagnostic work-up of the aqueous humor was carried out. Local production of specific antibodies against cytomegalovirus was identified in the aqueous humor. Topical treatment with antiviral and/or steroidal drugs was unsuccessful. The antiviral drug gancyclovir was applied systemically in two patients, but there was no impact on the corneal precipitates described. No intravitreal therapy was given. If these endothelial changes can be regarded as pathognomonic for cytomegalovirus infection, thorough slit lamp examination may be important for diagnosis of the presence of or the reactivation of cytomegalovirus infection in the eye. So far, no correlation has been found between the time course of corneal/endothelial precipitation and necrotizing retinitis.

Acquired Immunodeficiency Syndrome

[In vitro changes in the lens epithelium and corneal endothelium caused by the cytostatic drug daunomycin].

We evaluated the effects of the antiproliferative drug daunomycin on the viability and proliferation of cultured porcine lens epithelial cells. After a single short-term application, daunomycin penetrates the lens epithelial cells within 5 min. At a concentration of 2.5-7.5 mg/l, daunomycin has a low level of acute cytotoxicity and significantly suppresses the mitotic activity of the epithelial cells in culture. The daunomycin-induced endothelial lesions in freshly excised pig corneas were quantified with the Janus green photometry technique (n = 30) and studied with scanning electron microscopy (n = 9) in comparison to Ringer solution, which served as the control (n = 39). Whether the endothelial lesions were exposed to daunomycin or Ringer solution for 10 or 30 min seemed to make no significant difference. In addition, daunomycin did not seem to induce any morphological changes in the endothelial surface. These in vitro results confirm our clinical experience that daunomycin is apparently not harmful to the adult human corneal endothelium. Our results indicate that short-term endocapsular application of daunomycin during extracapsular cataract extraction, with or without IOL implantation, may prevent and/or delay the formation of capsular opacification.

Animals