The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.     

Emergence of West Nile virus lineage 2 in Europe: Characteristics of the first seven cases of West Nile neuroinvasive disease in horses in Austria

We report details of the first seven equine cases of confirmed West Nile neuroinvasive disease in Austria. The cases presented during summer and autumn of 2016 (n = 2), 2017 (n = 3) and 2018 (n = 2). All horses showed gait abnormalities and 6 of 7 horses exhibited fasciculations and/or tremors, and we provide video recordings of these. Three horses also showed cranial nerve involvement. Following rapid improvement, three horses were discharged. Four horses were euthanized due to the severity of clinical signs and subjected to neuropathological examination. West Nile virus (WNV) lineage 2 nucleic acid was detected in 5 of 7 horses, and WNV‐specific neutralizing antibodies in all 7 horses. In addition, serologic evidence of WNV infection was found in two out of fourteen in‐contact horses. Horses may be considered a sentinel species for human WNV infections, integrating human and veterinary medicine and thus contributing to the one health concept.     

Tactile Sensibility of Single‐Tooth Implants and Natural Teeth Under Local Anesthesia of the Natural Antagonistic Teeth

Introduction and Aim: The term osseoperception describes the capability of developing a subtle tactile sensibility over dental implants. The present clinical study aims at clarifying the question of how far tactile sensibility is to be attributed to the periodontium of the natural opposing tooth of the implant. Material and Method: Thirty‐two subjects with single‐tooth implants with natural opposing teeth were included in this clinical, single‐blind, split‐mouth study. The natural antagonistic tooth of the implant and the corresponding natural contralateral tooth were anesthetized with a locally infiltrated articaine anesthetic. In a computer‐assisted and randomized way, copper foils of varying thickness (0–100 µm) were placed interocclusally between the single‐tooth implant and the natural opposing tooth, and between the contralateral pair of natural opposing teeth in order to investigate the active tactile sensibility according to the psychophysical method of constant stimuli and evaluate it statistically by the Weibull distribution. Results: The average tactile sensibility of the implants with anesthetized antagonists at the 50% value calculated by means of the Weibull distribution was 20 ± 11 µm with a support area (90%–10% value) of 77 ± 89 µm. For the pair of natural teeth, the tactile sensibility at the 50% value was 16 ± 9 µm with a support area of 48.4 ± 93 µm. This resulted in an average intraindividual difference of 3.5 ± 7 µm at the 50% value and 29 ± 93 µm in the support area. The statistical calculations demonstrated an equivalent tactile sensibility (50% value) of the single‐tooth implant and the contralateral natural control tooth with the natural antagonists being anesthetized in each case (double t‐test, equivalence limit ± 8 µm, P < 0.01, power >80%). Conclusion: Apparently, the active tactile sensibility of single‐tooth implants with natural opposing teeth is not only to be attributed to the periodontium of the opposing tooth but also to a perception over the implant itself. This could support the hypothesis according to which the implant may have a tactile sensibility of its own.     

Thermal damage of the corneal endothelium in diode laser thermokeratoplasty

Laser thermokeratoplasty (LTK) can be applied for correction of hyperopia and astigmatism by means of concentrically placed coagulations. Because of the temperature rise during coagulation, damage of the endothelial cells directly below the irradiated areas is possible. In this study, we examined the extent of the thermally denatured zones for different laser parameters and the threshold of thermal endothelial damage as a function of of temperature and duration of elevated temperatures. The threshold for thermal damage of endothelial cells was determined in isotonic NaCl solution for temperature exposures of 10 s and 1 min in a water bath. To determine the damage zones, corneas were irradiated under standardized conditions with a continuously emitting infrared (cw-IR) laser diode at various wavelengths and different power values and were stained after preparation with trypan blue and alizarine red. The extensions of the damage zones were compared with calculated isotherms. Fifty percent cell damage was found at temperatures of 65 °C for heating times of 10 s and at 59 °C for 1 min. With thicker corneas, less laser power and higher absorption coefficients, the damage zone was reduced. The damage range determined corresponded to the calculated isotherms of 60 °C and 70 °C. Regarding clinical LTK, a loss of endothelial cells can be predicted and minimized or totally avoided by choosing the appropriate irradiation parameters.     

Division of viscoelastic substances for ophthalmological surgery

Individual properties of a viscoelastic substance for ophthalmologic applications are intimately tied to its chemical and rheologic characteristics. Independent comparative data for vicoelastic substances are not readily available or interpretable. Material and methods: Twenty-six different commercially available viscoelastic substances were investigated using the Advanced Rheometric Expansion System and the Rheometric Scientific 800 device to analyze elastic and viscous modulus, complex viscosity (dynamic frequency dependance) and viscosity at the zero shear rate by extrapolation using the Ellis fit. Results: Viscosity (cps) at zero shear rate (s^–1, mean of six different samples): Sodium hyaluronate products: Amivisc Plus: 128; AMO Vitrax: 41; Biolon: 243; Dispasan: 130; Dispasan Plus: 782; Healon: 243; Healon GV: 2451; Healon 5: 5525; Microvisc (Morcher Oil): 1162; Microvisc Plus: 3663; Morcher Oil: 1253; Provisc: 207; Rayvisc: 78; Viscoat: 58; Viscorneal (Allervisc): 733; Viscorneal Plus (Allervisc Plus): 1176; Visko: 206; Visko Plus: 1683. Hydroxypropylmethylcellulose (HPMC) products: Acrivisc: 7; Adatocel: 8; Coatel: 6; HPMC Ophthal H: 94; HPMC Ophthal L: 7; Ocucoat: 6; PeHa-Visko: 5; Visco Shield: 60. Conclusion: Sodium hyaluronate as well as HPMC viscoelastic substances demonstrated remarkable differences in rheological properties from each other. In some cases, the results of this independent investigation differed from the values provided by the companies. A new division of commercially available viscoelastic substances into subgroups is presented, which provides a scientific base for various practical viscosurgical aspects. These real rheologic properties of each substance allow the ophthalmic surgeon to choose the viscoelastic substance that is most suitable for the surgical situation.     

Diode laser thermokeratoplasty – first clinical experience

Purpose: Pulsed holmium lasers are currently used to correct hyperopia by means of laser thermokeratoplasty (LTK). Series of μs laser pulses are applied with a high repetition rate to induce shrinkage of corneal collagen fibers. The pulsed energy application results in intrastromal temperature peaks of up to 200 °C. A continuously emitting laser diode can – as we demonstrated recently in an invivo study on minipigs – be used for LTK and may be of advantage because the temperature rise is more steady. The aim of this study was to examine the safety, amount, and stability of hyperopic correction of diode LTK on blind human eyes. Methods: We used a laserdiode that was set to continuously emit light at λ = 1.854 μm/μ_a = 1.04 mm^–1(group I, n = 4) or 1.87 μm/μ_a = 1.92 mm^–1 (group II, n = 4). Radiation energy was 100 to 150 mW for 10 s per coagulation. Eight coagulations on a single ring (group I) and 16 coagulations on a double ring (group II) diameter were applied in the cornea concentric to the entrance pupil by means of a vacuum-fixed application mask (group I = conjunctival fixation; group II = corneal fixation) and a handpiece with a focusing optic. Preoperatively as well as 1 week, 1, 2, 3, 6 12 and 18 months postoperative ophthalmologic controls were performed and the corneal refractive power was measured. Results: In group I initial refractive changes of up to + 4.9 D were achieved (1 week postoperative). However, due to the great penetration depth of the laser irradiation, large endothelial defects resulted beneath the stromal coagulations. In group II an initial refractive change of up to + 6.8 D was achieved and as a result of the reduced penetration depth, the endothelial cell damage was much reduced. Partial regression of the refractive effect occured in all subjects, which continued in higher refractive changes during the 2^nd postoperative year. The refractive effect at 12 months was + 0.6 to + 1.5 D in group I and + 0.9 to + 5.7 D in group II. At 12 months the induced astigmatism was 0.5 to 2.2 D in group I and 0.3 to 1.6 D in group II. No serious adverse effects were noticed. Conclusion: A continously emitting laser diode working at a wavelength of 1.87 μm can be used to correct hyperopia by means of LTK safely and effectively. Regression occurs predominantly in the first 6 postoperative months. Further studies must be conducted to determine the importance of patient inherent parameters such as age in establishing a nomogram.      

Evaluation of polyurethane stent implantation for the treatment of complete obstruction of the nasolacrimal system: 8-month follow-up and complications

Dacryocystorhinostomy is still the standard procedure complete stenosis of the nasolacrimal duct. New methods try to preserve the natural lacrimal pathway. Song implanted in 1995 a nasolacrimal polyurethane stent through the nasolacrimal duct. The results and complications of this new method are described in this prospective study. METHODS: Thirty consecutive patients with complete obstruction of the nasolacrimal duct or lacrimal sac were included in the study. The stenosis was localized by dacryocystography. The ages ranged from 22 to 87 years (mean, 58.9 +/- 16 years). Dacryocystography was performed immediately, 4 weeks and 8 months after the procedure to verify the position and patency of the stent. RESULTS: Twenty-five short (35 mm) and 5 long (45 mm) stents were implanted. Twenty-four of 30 patients after 4 weeks and 9 of 10 patients after 8 months had reduced or no complaints. In 1 patient the stent was obstructed. Forceful irrigation with saline solution permitted recanalization. In 1 patient the stent had moved into the upper canaliculus. Because of irritation of the canaliculus it had to be pulled out after 2 months. CONCLUSION: The follow-up is still too short to recommend stent implantation as a real alternative to dacryocystorhinostomy. The main advantages are that the procedure is faster, no incision is necessary, and the local anesthesia is easier. The disadvantage is the need for X-ray examination.     

Bath-water PUVA therapy with 8-methoxypsoralen in mycosis fungoides

PUVA therapy is widely used for early stage mycosis fungoides. While the efficacy of PUVA with oral 8-methoxypsoralen (8-MOP) is well documented, the use of its topical variation, bath-water PUVA therapy with 8-MOP has not been studied. The purpose of this study was to assess the effect of 8-MOP bath-water PUVA therapy in adult patients with early stage mycosis fungoides. We retrospectively evaluated the outcomes of bath-water delivery of 8-MOP (1 mg l(-1)) in 16 patients with early stage mycosis fungoides. In all patients complete response was achieved after a mean duration of 63 days requiring 29 treatments and a mean cumulative UVA dose of 33 J cm(-2). The time to relapse after complete clinical clearance was 45.6 (+/-9.2) weeks. In comparison, oral PUVA therapy with 8-MOP resulted in complete response after 64.5 days (25.8 treatments) with a mean relapse-free period of 30 (+/-3.5) weeks. We conclude that bath-water PUVA therapy with 8-MOP is a valuable photo-therapeutic alternative, which should be considered for patients in whom systemic psoralen cannot be used.     

The consequences of delayed intervention when treating chemical eye burns

Background Immediate rescue intervention for chemical and thermal eye burns can save the victim’s sight. We studied the anterior chamber pH changes immediately after ex vivo eye burn to investigate the effects of immediate and delayed intervention. Methods Twenty three enucleated pigs eyes were burnt with 500 μl 2 mol NaOH for 20 s using a cylinder with a diameter of 10 mm. The corneas were rinsed in groups with 1015 ml ordinary tap water at a flow rate of 1.125 ml/s for 15 minutes immediately after burning (n = 6), and after a delay of 20, 40, and 60 s (n = 5, 3 and 4 respectively). One group of eyes was not rinsed (n = 5). The intraocular pH was defined at the start as ‘min pH’ and the end as ‘max pH’(ΔpH = max pH-min pH). Results The intraocular pH increased sharply in the untreated eyes from a min pH of 6.76 ± 0.55 to a max pH of 11.85 ± 0.24, yielding a ΔpH of 5.08. The difference between the timepoint at which the pH began to increase and the speed of change was significantly different between the unrinsed and rinsed eyes, and there was an inverse correlation between this and the time at which rinsing started (p < 0.001). The best results were achieved in eyes rinsed immediately after burning (p < 0.001). The pH in the eyes not rinsed immediately increased rapidly, and in all groups in which rinsing was delayed the max pH was markedly higher (p = 0.093). Conclusions Immediate emergency rinsing is essential in eye burn victims. Appropriate rinsing solutions and treatment facilities in the form of rinsing stations where chemical burns may occur must be available at the workplace. Tap water is also effective as a rinsing solution. Presentation The results were the subject of a short oral presentation at the 104th DOG Annual Meeting 2006 in Berlin.     

Endothelin receptor B in trabecular meshwork

Endothelin-1 (ET-1), the most potent vasoconstrictor known to date, seems to be involved in the pathogenesis of primary open angle glaucoma. ET-1 was found in different tissues of the eye and in high concentrations in the aqueous humour. The effects of ET-1 are mediated by two receptors, ET-A receptor (ET-AR) and ET-B receptor (ET-BR), which are both expressed in bovine trabecular meshwork (TM). ET-1 induced contraction of TM predominantly by activation of ET-AR. This study analyzes the role of ET-BR in TM function and investigates the synthesis of ET-1 by human TM (HTM) cells. The effect of IRL-1620, a specific ET-BR agonist, on contractility of bovine TM (BTM) was investigated with a force length transducer system. The effect of this agonist on intracellular free Ca(2+) [Ca(2+)](i) was examined using the Ca(2+)-sensitive dye fura-2AM. The expression of the ET-AR and ET-BR was investigated in cultured HTM cells using Western blot and PCR methods. With PCR methods the expression of prepro-endothelin-1 (ppET-1) and isoforms of endothelin-1 converting enzyme (ECE-1) in cultured HTM cells was analyzed. Activation of ET-BR by IRL-1620 (5 x 10(-7)M) results in contraction of native BTM (41% of the carbachol value) and also in a transient increase in [Ca(2+)](i) in cultured BTM and HTM cells (365 and 273% of the basal level, respectively). IRL-1620 also induced contraction in native BTM under intra- and extracellularly Ca(2+)-free conditions. A clear signal for ET-AR at 40 kDa and ET-BR at 35 kDa could be detected in membrane lysates of cultured HTM cells. PCR analysis further confirmed the existence of ET-AR and ET-BR in these cells. Furthermore, RT-PCR revealed that neither ppET-1 nor one of the ECE-1 isoforms was expressed in cultured HTM cells. This study presents evidence for the expression of a functional ET-BR in bovine and human TM. Currently, there is no evidence for ET-1 synthesis in HTM cells. Further investigations are necessary to clarify the physiological function of ET-BR in TM and the source of ET-1 at this tissue.