"OSMO-UT-DSAEK" using THIN-C medium.

BACKGROUND: When performing ultra-thin Descemet's stripping automated endothelial keratoplasty (UT-DSAEK), the quality of the stromal interface and stromal thickness seem to be critical for visual outcome. The aim of this study was to investigate whether additional osmotic deswelling prior to UT-DSAEK improves the quality of the cut surface and leads to a more reliable and deeper cut in UT-DSAEK ("OSMO-UT-DSAEK"). METHODS: Seventeen human donor corneas not usable for transplantation were used in this experiment. After standard deswelling with culture Medium II, ten corneas were randomly assigned to be additionally deswollen within THIN-C medium. The other remaining seven corneas were put back into culture Medium II. All corneas were placed in an artificial anterior chamber system (Moria); a double path cutting procedure using a microkeratome (Moria) was then performed. Corneal thickness was measured by ultrasound biomicroscopy and in paraffin-embedded slides, followed by histological grading of the cut surface. RESULTS: Stromal interface smoothness significantly improved after preconditioning in THIN-C medium (Pearson P = 0.019). The correlation of the corneal thickness obtained by UBM (mean 706 ± SD 208 µm) and histology (mean 530 ± SD 159 µm) was not significant (Pearson r = 0.11, P > 0.05, mean difference 247, 95 % CI [+50;+304]). We found no significant correlation between the microkeratome setting and the actual thickness of the lenticule measured in histological analysis in both media as well as for the first and second cut (first cut: Pearson r = 0.9, P = 0.1, 95 % CI [-10;+96], second cut: Pearson r = 0.9, P = 0.4, 95 % CI [-10;+22]). CONCLUSION: Preconditioning of corneas with THIN-C medium significantly improved the quality of the graft interface in UT-DSAEK, but did not significantly improve the cut precision of the microkeratome.

[Anti(lymph)angiogenic preconditioning prior to keratoplasty]. / Antiangiogene Präkonditionierung vor Keratoplastik.

PURPOSE: The aim of this study is to describe novel therapeutic concepts to promote graft survival in high-risk keratoplasty by targeting (lymph)angiogenesis in the transplant context. METHODS: A PubMed literature search and our own clinical and experimental data are evaluated. RESULTS: There are three options for anti(lymph)angiogenic preconditioning: a) primary prevention of neovascularisation during the disease process, b) secondary prevention by regressing established blood vessels prior to transplantation and (c) tertiary prevention through inhibition of post-keratoplasty neovascularisation. CONCLUSION: Modern topical anti(lymph)angiogenic therapies seem to be able to reduce the risk of graft rejection especially in high-risk keratoplasty.

Sustained high demand for intensive care unit resources for the treatment of burn patients during the COVID-19 pandemic in Northern Germany: A single-centre cross-sectional study.

Introduction: The ongoing COVID-19 pandemic caused by SARS-CoV-2 has changed everyday life worldwide. To reduce disease transmission, governments introduced various policies such as social distancing, stay-at-home orders, and travel restrictions. The goal of this study was to investigate the characteristics of burn patients admitted to the burn intensive care unit before and during the COVID-19 pandemic. Patients and methods: A retrospective descriptive analysis of the hospital's burn registry was performed from 1 March 2019 until 1 January 2022. Results: A total of 326 patients were included in this study. Eighty-eight patients presented before and 238 patients during the COVID-19 pandemic. The majority of burns occurred during private incidents (80% [2022], 92% [2020]), and burns were most frequently caused by flames (24% [2022], 32.99% [2021]). Work-related injuries occurred less frequently (7.76% [2020], 20% [2022]). Constant results were obtained regarding severity and total body surface area affected (1-80%). Conclusion: This study highlights high numbers of burn patients admitted to the burn intensive care unit before and during the COVID-19 pandemic. Consequently, burn intensive care units must retain their special position within the national health system and should not be included in resource relocation during the prioritisation of intensive care resources. Multicentre studies should focus on the national impact of COVID-19 on the treatment of burn patients.

[Technical aspects of quality assurance for intravitreal injections (IVI)]. / Technische Umsetzung der Qualitätssicherung bei der intravitrealen operativen Medikamenteneingabe (IVOM).

BACKGROUND: Successful quality assurance in intravitreal injection (IVI) of medications requires a complex information technology infrastructure. The main challenges are data availability independent of location, standardization of clinical data, integration of extensive and currently non-standardized image documentation from coherence tomography and compliance with data protection regulations. OBJECTIVE: In this article the technical implementation and data protection principles are reviewed. MATERIAL AND METHODS: Essential aspects in the implementation of quality assurance in the field of IVI are discussed in a systematic approach. RESULTS: In the field of network architectures web-based applications supplemented by local virtual private networks (VPN) and/or other software instances have recently replaced the previously commonly used physical data medium exchange. The standardization of the data, e.g. by converting the visual acuity into logMAR, plays an important role in the collection of treatment data. Multiple non-standardized data formats in optical coherence tomography complicate the general quality assurance structure and comparability of data. CONCLUSION: International standards will probably facilitate this in the near future. Until then individual solutions have to be found on site.

[10 years of Descemet membrane endothelial keratoplasty in Fuchs endothelial corneal dystrophy : What have we learned?] / Zehn Jahre "Descemet membrane endothelial keratoplasty" bei Fuchs-Dystrophie : Was haben wir gelernt?

BACKGROUND AND OBJECTIVE: Descemet membrane endothelial keratoplasty (DMEK) has increased in popularity since its introduction over 10 years ago. This article presents a summary of the experiences of the past years collected at the Department of Ophthalmology at the University of Cologne. METHODS: A literature review of DMEK studies primarily from the Department of Ophthalmology at the University of Cologne, Germany was carried out. Own experiences in the fields of donor selection and graft preparation, DMEK surgery, complication management and postoperative treatment are summarized. RESULTS: Since the introduction of DMEK experience has been gained and ongoing improvements have occurred ranging from donor-recipient allocation to postoperative follow-up. These led to a better reproducibility of the intervention for the surgeon, to a better postoperative result and to a reduction of the complication rate. DISCUSSION: The DMEK represents a safe and individualized procedure for endothelial transplantation for corneal endothelial dysfunction. Continuing development of the method leads to optimization and safer results.

[Results of Cutler-Beard procedure for reconstruction of extensive full thickness upper eyelid defects following tumor resection]. / Ergebnisse nach Cutler-Beard-Plastik zur Rekonstruktion ausgedehnter Oberliddefekte nach Tumorexzision.

BACKGROUND: The Cutler-Beard bridge flap technique is an established method for reconstruction of large full thickness upper eyelid defects. The purpose of the present study was to report experiences with the surgical technique, complications and results of this cutaneoconjunctival flap procedure following tumor resection. PATIENTS AND METHODS: A total of 18 patients with extensive full thickness upper eyelid defects after tumor excision underwent a Cutler-Beard procedure. Of the patients four received an additional eye bank scleral implant and one received an additional free tarsal graft from the fellow upper eyelid to enhance eyelid stability. RESULTS: The Cutler-Beard bridge flap technique was surgically feasible in all patients without causing damage to the lower eyelid bridge or resulting in any infections. Out of the 13 reconstructions without additional stabilizing tissue 3 (23%) developed an upper eyelid entropion that was successfully managed using a secondary scleral implant. None of the five reconstructions using additional scleral or tarsal tissue showed an entropion of the upper eyelid. CONCLUSION: The Cutler-Beard bridge flap technique, which can be combined with grafting additional stabilization tissue in defects exceeding 75% of the upper eyelid length, is a reliable method for reconstruction of large full thickness upper eyelid defects following tumor excision.

[Boston-keratoprosthesis : Preliminary experiences in 13 high-risk eyes from the Department of Ophthalmology of the University of Cologne]. / Boston-Keratoprothese : Erste Erfahrungen bei 13 Hochrisikoaugen aus der Kölner Universitätsaugenklinik.

BACKGROUND: Corneal transplantation in high-risk eyes remains a challenge. The Boston keratoprosthesis (B-KPro) is a final option for patients with end-stage corneal disease and a poor prognosis with conventional penetrating keratoplasty. In this article the results of the first 13 eyes that received a B-KPro type I at the Department of Ophthalmology, University of Cologne, Germany are reported and the usefulness of postoperative slit-lamp optical coherence tomography (SL-OCT) for control purposes is evaluated. MATERIAL AND METHODS: All recipients of a B-KPro type I between September 2013 and May 2015 were included in the study. The feasibility of the operation, clinical outcomes, complications and revision surgery were investigated. The visualization of wound healing by SL-OCT was analyzed. RESULTS: The age of the patients ranged from 26 to 92 years (mean 57.3 ± 20.9 years). In all 13 eyes from 12 patients (6 males and 6 females) dense corneal opacification with vascularization and sometimes also conjunctivalization was present. Preoperative visual acuity was reduced and ranged from mere light perception up to a maximum of 1/35 eye chart. All 13 eyes could be supplied with a B-KPro type I without any intraoperative complications, in 6 eyes no significant postoperative complications occurred, whereas in 7 eyes various additional surgical interventions were required and 1 B-KPro could not be preserved. Postoperative visual acuity ranged from light perception to 20/32 and was significantly improved in 85 % of the treated eyes. The use of SL-OCT reproducibly allowed the postoperative assessment of stromal thinning. CONCLUSION: The B-KPro provides the possibility of visual rehabilitation in high-risk eyes that could never be achieved without artificial cornea replacement. Despite higher complication rates this technique represents a significant progress in the surgical treatment of complex corneal pathologies. Regular and intensive postoperative controls are necessary to achieve good long-term results.

Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations.

Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome ("secretome"), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) ß, and an impact on matrix processing enzymes. Functionally, FAPα mildly induces sprout formation by human umbilical vein endothelial cells. Moreover, loss of FAPα leads to a more epithelial cellular phenotype and this effect was rescued by exogenous application of TGFß. In collagen contraction assays, FAPα induced a more contractile cellular phenotype. To characterize the proteolytic profile of FAPα, we investigated its specificity with proteome-derived peptide libraries and corroborated its preference for cleavage carboxy-terminal to proline residues. By "terminal amine labeling of substrates" (TAILS) we explored FAPα-dependent cleavage events. Although FAPα acts predominantly as an amino-dipeptidase, putative FAPα cleavage sites in collagens are present throughout the entire protein length. In contrast, putative FAPα cleavage sites in non-collagenous proteins cluster at the amino-terminus. The degradomic study highlights cell-contextual proteolysis by FAPα with distinct positional profiles. Generally, our findings link FAPα to key aspects of CAF biology and attribute an important role in tumor-stroma interaction to FAPα.

Distribution of serotonin and dopamine receptors in Aplysia tissues: analysis by [3H]LSD binding and adenylate cyclase stimulation.

The distribution of receptors for serotonin and dopamine has been studied in various neuronal and non-neuronal tissues from Aplysia californica using: (1) a [3H]LSD binding assay; and (2) stimulation of adenylate cyclase activity. High levels of specific [3H]LSD binding were found in all ganglia and nerves examined. Lower levels of binding were present in a number of muscle tissues and in the sheath surrounding the central ganglia. The ability of serotonin and dopamine to inhibit [3H]LSD binding depended upon the tissue examined. In muscle tissue, most of the binding was sensitive to serotonin. In contrast, a number of ganglia (e.g. the pleural, abdominal or cerebral) contained a considerable proportion of dopamine-sensitive binding. A limited pharmacological analysis of serotonin-sensitive [3H]LSD binding indicated that Aplysia serotonin receptors are closely related to those found in the snail, Helix pomatia, and in rat brain. Adenylate cyclase activity in membranes from Aplysia ganglia, muscles and connective nerves was stimulated by serotonin (but not by dopamine). The amount of serotonin-sensitive adenylate cyclase correlated well with the amount of serotonin-sensitive [3H]LSD binding in most tissues. D-LSD was a partial agonist on the serotonin-sensitive adenylate cyclase, whereas the pharmacologically inactive stereoisomer L-LSD was without effect. The high density of serotonin receptors in pleuro-abdominal connective nerves, and their presence in the connective tissue sheaths surrounding the ganglia, suggests that not all of these receptors are located at synapses. On the other hand, the tissue distribution of dopamine and serotonin receptors, as measured by these techniques, is consistent with that expected from electrophysiological data.

Regression of mature lymphatic vessels in the cornea by photodynamic therapy.

BACKGROUND: Corneal (lymph) angiogenesis is a predominant risk-factor for immune rejection after transplantation. Techniques to regress pre-existing pathological corneal lymphatic vessels prior to transplantation are missing so far. Therefore we analysed the possibility to regress corneal lymphatic vessels by photodynamic therapy (PDT), after intrastromal verteporfin injection. METHODS: Combined hemangiogenesis and lymphangiogenesis was induced in female BALB/c mice using the murine model of suture-induced inflammatory neovascularisation. Thereafter, the treatment group received an intrastromal injection of verteporfin (controls: phosphate buffered saline (PBS)) followed by PDT. Corneas were excised at different time points (1 day, 5 days and 10 days) after PDT and corneal whole mounts were stained with CD31 and LYVE-1 to quantify hemangiogenesis and lymphangiogenesis. RESULTS: Whereas blood vessels showed no significant reduction after PDT, lymphatic vessels could significantly be reduced with PDT after intrastromal verteporfin injection: 1 day after PDT, lymphatic vessels were reduced by 62% (p=0.20). After 5 days and 10 days, lymphatic vessels were reduced by 51% and 48% (p<0.001), respectively. CONCLUSIONS: This study for the first time shows that PDT after corneal intrastromal verteporfin injection can selectively regress lymphatic vessels. This may become a new 'preconditioning strategy' to reduce pre-existing corneal lymphatic vessels prior to transplantation and thereby reduce allograft rejection in high-risk patients.

Effects of domestic wastewater on serum enzyme activities of brown trout (Salmo trutta).

1. Chronic injuries of kidney and liver tissue of brown trout caused by domestic wastewater were not accompanied by increased activities of serum enzymes (GOT, GPT). 2. Increased enzyme activities were only observed in fish with acute Saproloegnia infection. 3. It is important to distinguish between acute and chronic responses of serum enzymes in diseased fish.

Isolation of biochemical mutants using haploid mesophyll protosplasts of Hyoscyamus muticus : IV. Biochemical characterisation of nitrate non-utilizing clones.

Four nitrate non-utilizing clones of Hyoscyamus muticus, obtained by a total isolation method, possess all the known characteristics of cnx-type nitrate-reductase-deficient variants: 1) strict dependence on a reduced nitrogen source such as a mixture of amino acids; 2) chlorate resistance; 3) normal nitrate uptake; 4) lack of nitrate-reductase and xanthine-dehydrogenase activities, but presence of cytochrome-c-reductase and nitrite-reductase activities; 5) in vitro nitrate-reductase complementation with a molybdenum cofactor source. Two of the clones (MA-2 and I2D12) are molybdate repairable in vivo, whilst the other two clones (VIC2 and XIVE9) are not.

Isolation of biochemical mutants using haploid mesophyll protoplasts of Hyoscyamus muticus : I. A NO 3 (-) non-utilizing clone.

A population of 3070 clones derived from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated mesophyll protoplasts of haploid Hyoscyamus muticus was tested for amino-acid auxotrophy without enrichment. One clone (MA-2) was stably and specifically dependent on casein hydrolysate and could be fed also by a number of single amino acids or by other reduced nitrogen sources. MA-2 was found to be chlorate resistant and devoid of in vivo nitrate reductase activity under inductive conditions. Permissive and restrictive growth conditions for MA-2 were investigated more closely and media were found promoting morphogenesis. Selection and testing of clones were complicated by an unspecific growth stimulation of some wild type cultures by amino acids, thiamine and m-inositol.

d-[3H]Lysergic acid diethylamide binding to serotonin receptors in the molluscan nervous system.

d-[3H]Lysergic acid diethylamide (LSD) bound to both dopamine- and serotonin (5HT)-sensitive sites in a particulate fraction derived from the central nervous system of the snail Helix pomatia. Conditions were found which enabled the two sites to be studied independently. [3H]LSD appeared to have a slightly higher affinity for dopamine-sensitive binding (Kd = 0.5 nM) than for 5HT-sensitive binding (Kd = 1.2 nM). A pharmacological analysis of the binding indicated that while dopamine- and 5HT-related agonists clearly discriminated between the two sites, putative antagonists showed little specificity for dopamine- or 5HT-sensitive binding. The pharmacology of 5HR-sensitive [3H]LSD binding was studied in relation to a 5HT-sensitive adenylate cyclase present in a particulate fraction derived from the same tissue. There was a very good correlation between the abilities of a range of agents to act as agonists or antagonists in the 5HT-sensitive adenylate cyclase assay and their abilities to displace 5HT-sensitive [3H]LSD binding (r = 0.94; p less than 0.001). In particular, d-LSD and a number of neurologic drugs were inhibitory in both assays in a stereoselective manner. These data suggest that in molluscan tissues, 5HT-sensitive [3H]LSD binding is related to the 5HT receptor which is coupled to adenylate cyclase.

Predicting psychologic responses to orthognathic surgery.

A longitudinal study was conducted of the psychologic characteristics of 74 persons undergoing orthognathic surgery. The effects of neuroticism, locus of control, and expectations upon postsurgical outcomes were examined. The majority of patients scored in the normal range of most personality variables. The findings suggest a generally intact ego and accurate self-concept among orthognathic surgery patients. Expectations of pain and parasthesia were the best predictors of postsurgical outcomes, while neuroticism and locus of control scores predicted some outcomes in the early postoperative stages. The results indicate the importance of preparing orthognathic surgery patients against unrealistic expectations before surgery is undertaken, and of counseling certain patients during the early postoperative period.