[Monochromatic aberration in accommodation. Dynamic wavefront analysis]. / Aberrationen höherer Ordnung bei Akkommodation. Dynamische Wellenfrontmessung.

BACKGROUND: Monochromatic aberrations may influence the visual acuity of the eye. They are not stable and can be affected by different factors. The subject of the following paper is the dynamic investigation of the changes in wavefront aberration with accommodation. METHOD: Dynamic measurement of higher and lower order aberrations was performed with a WASCA Wavefront Analyzer (Carl-Zeiss-Meditec) and a specially constructed target device for aligning objects in far and near distances on 25 subjects aged from 15 to 27 years old. RESULTS: Wavefront aberrations showed some significant changes in accommodation. In addition to the characteristic sphere reaction accompanying miosis and changes in horizontal prism (Z(1) (1)) in the sense of a convergence movement of the eyeball also occurred. Furthermore defocus rose (Z(2) (0)) and astigmatism (Z(2) (-2)) changed. In higher-order aberrations a decrease in coma-like Zernike polynomials (Z(3) (-1), Z(3) (1)) was found. The most obvious change appeared in spherical aberration (Z(4) (0)) which increased and changed from positive to negative. In addition the secondary astigmatism (Z(4) (-2)) and quadrafoil (Z(4) (4)) rise also increased. The total root mean square (RMS), as well as the higher-order aberrations (RMS-HO) significantly increased in accommodation which is associated with a theoretical reduction of visual acuity. An analysis of the influence of pupil size on aberrations showed significant increases in defocus, spherical aberration, quadrafoil, RMS and RMS HO by increasing pupil diameter. By accommodation-associated miosis, the growing aberrations are partially compensated by focusing on near objects. Temporal analysis of the accommodation process with dynamic wavefront analysis revealed significant delays in pupil response and changing of prism in relation to the sphere reaction. In accommodation to near objects a discrete time ahead of third order aberrations in relation to the sphere response was found. CONCLUSION: Using dynamic wavefront measurement achieved a sequential analysis of aberrations during accommodation. Significant changes in the lower and higher-order aberrations could be detected. These are additionally varied by the associated pupillary response. Moreover, the synchronicity of wave front reaction in the accommodation process was proven.

SEMG activation patterns of thigh muscles during upright standing in haemophilic patients.

Although electromyography (EMG) is a common method to evaluate muscle activity, studies utilizing EMG in haemophilic patients are rare. The haemophilic arthropathy, resulting in altered afferent information is expected to cause disturbed activation and inter-muscular coordination patterns in haemophilic subjects. The aim of this study was to determine differences of selected knee muscles between haemophilic patients and non-haemophilic subjects during upright standing. Surface EMG (SEMG) amplitudes of rectus femoris, vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF) muscles of both sides were measured in 27 haemophilic patients (H) and 26 control subjects (C) while standing on an even surface. Data from both sides were pooled in C, but data of H were subdivided further according to major (H-MA) and minor (H-MI) affected joints. To normalize the data, amplitude ratios (percentage of cumulated activity) were calculated as well. Regardless of whether H-MA or H-MI was compared with C, amplitudes of all extensor muscles reached significantly higher levels in H (P < 0.05). SEMG amplitude ratios also differed between H and C. Independent of subgroup, BF showed significantly reduced activation ratios (P < 0.01). Only the ratios of VM and VL of H-MA could replicate the observed amplitude differences to C (P < 0.05). These findings show that while standing, haemophiliacs maintain the necessary stability demands through increased extensor activities and modulated coordination patterns. Although all thigh muscles of haemophiliacs are characterized by distinct atrophy, increased amplitude levels could be proved for the knee extensor muscles only. Therefore, general atrophy-related effects cannot explain these results.

[The influence of eye movements on monochromatic wavefront aberrations]. / Aberrationen höherer Ordnung bei Blickbewegungen.

BACKGROUND: Wavefront-guided corneal surgery is a standard therapeutic option for correcting refractive errors. If the wavefront measured preoperatively is influenced by an incorrect alignment of the bulb, the ablation profile could be distorted and the quality of vision reduced. METHOD: Wavefront analysis was done on 49 eyes, examining the primary gaze of the bulb as well as abduction, adduction, elevation, and depression. RESULTS: The study demonstrated a significant influence of eye movements on astigmatic aberrations. Horizontal eye movements have a stronger influence than vertical ones do. Adduction especially leads to changes; here, RMS showed a significant difference. CONCLUSIONS: Eye movements have a significant effect on wavefront profiles. The amount of aberration induced is generally very low. In individual cases, the numbers of aberrations induced by eye movements are in ranges reported to reduce the postoperative quality of vision when the ablation profile is taken into account.

Trough levels of mycophenolic acid and its glucuronidated metabolite in renal transplant recipients.

OBJECTIVE: The prophylactic use of the immunosuppressant prodrug, mycophenolate mofetil (MMF) to prevent graft rejection in renal transplant patients is continuing to increase. We measured trough levels of the active metabolite, mycophenolic acid (MPA) and its inactive glucuronide (MPAG) in renal recipients with the aim of characterizing individual variability and of ascertaining factors influencing trough levels, in particular the effect of differences in renal function and the effect of drugs given concurrently. METHODS: Laboratory and clinical data obtained in 35 renal recipients treated with triple therapy (MMF, cyclosporin A (CsA), steroids) were included in this retrospective study. Trough levels of MPA and MPAG were obtained after transplantation and up to 16 months post transplantation where the mean observation period was 5.7 months. Plasma levels were measured using a validated HPLC assay. RESULTS: A total of 212 plasma concentrations of MPA and 209 of MPAG were measured. There was considerable intra- and interindividual variability in MPA and MPAG trough levels especially in the early post-transplantation phase. At a fixed dose of 2 g/d MMF, the mean MPA level during the first 30 days averaged 1.46 +/- 1.31 microg/ml vs. 1.87 +/- 0.89 microg/ml after 30 days and later (p = 0.130) and the mean MPAG concentration averaged 188.1 = 142.8 [microg/ml vs. 98.09 +/- 52.4 microlg/ml (p 0.003). The MPAG levels were positively correlated with the serum creatinine concentrations (r = 0.815, p < 0.001), and in the case of MPA there was a correlation with the serum protein concentrations (r = 0.258, p = 0.001). Concomitant drug treatment using CsA, steroids and furosemide were without effect of the measured plasma concentrations, but in the case of xipamide (+) and diltiazem (-) an effect on MPA and MPAG levels and a co-effect depending on the serum creatinine could not be excluded. Neither CsA trough levels nor hemoglobin levels were related to MPA and MPAG trough levels. CONCLUSIONS: The data of this study demonstrate that there is substantial individual variability in the trough levels of MPA and MPAG after renal transplantation which may be associated with the functional status of the graft and the serum protein level. Whether comedication with xipamide and diltiazem affects the plasma levels of MPA and MPAG remains to be clarified in further investigations.

Post-operative hypoalbuminaemia and procalcitonin elevation for prediction of outcome in cardiopulmonary bypass surgery.

BACKGROUND: Because few studies have addressed postoperative hypoalbuminaemia in relation to hospital mortality, we evaluated this association and the prognostic value of increased procalcitonin (PCT) after cardiopulmonary bypass (CPB) surgery. METHODS: In 454 consecutive patients undergoing CPB, minimal serum albumin, colloid osmotic pressure (COP) and maximal PCT were retrospectively obtained from the 2nd to 10th postoperative day. Receiver operating characteristic (ROC) and multiple regression analyses determined independent predictive strength for 28-day mortality from preoperative albumin, Euroscore, postoperative minimal albumin and COP, and maximal PCT. Cut-off points for the four strongest predictors were calculated by the area under the curve (AUC) in the ROC for the 28-day mortality. RESULTS: Maximal PCT showed the largest AUC (0.85; 95% CI 0.79-0.90) and the highest relative risk (RR 12.17; 95%CI 5.26-28.16; P < 0.001), compared with postoperative albumin (AUC 0.72; 95% CI 0.62-0.81; RR 5.35; 95%CI 2.99-9.56; P < 0.001) and EuroSCORE (AUC 0.73; 95%CI 0.63-0.83; RR 4.48; 95%CI: 1.78-11.28; P < 0.01). By logistic regression, postoperative albumin was the strongest predictor of mortality (odds ratio 0.86; 95% CI 0.84-0.89). Cut-off values for predicting 28-day mortality were found for postoperative albumin and PCT at 17.8 g l(-1) and 2.5 ng l(-1), respectively. A slight but significant inverse correlation between PCT and albumin was found. Patients with albumin less than the cut-off showed significantly higher median values for PCT levels (2.5 vs. 1.0 g l-1), a higher 28-day mortality rate (20.8% vs. 4.5%), and a longer ICU stay (6 vs. 3 days) in comparison with patients with minimal albumin greater than 18 g l(-1). CONCLUSIONS: Post-operative serum albumin <18 g l(-1) and PCT >2.5 ng l(-1) are predictive for a higher 28-day mortality rate in cardiosurgical patients. Both peak PCT and minimal albumin were better outcome predictors than the Euroscore, which better represents the preoperative condition of the patient.

Butyrylcholinesterase in lumbar and ventricular cerebrospinal fluid.

OBJECTIVES: This study establishes reference data for human lumbar CSF butyrylcholinesterase (E.C.3.1.1.8.) activity and investigates the enzyme activity in ventricular CSF. We comment on the relationship between CSF butyrylcholinesterase activity and other laboratory parameters. SUBJECTS AND METHODS: We investigated 64 lumbar CSF samples obtained from a clinically healthy population and 169 ventricular CSF samples collected from 90 neurosurgical patients. RESULTS: The reference range we recommend for lumbar CSF butyrylcholinesterase activity is 5.4 to 17.0 nmol/min x ml. The majority of ventricular butyrylcholinesterase activities in our patient subset ranged up to 5 nmol/min x ml. CONCLUSIONS: We established the relative influence of serum and CNS components on total CSF butyrylcholinesterase activity. The CNS fraction predominates the total butyrylcholinesterase activity in normal lumbar CSF. In ventricular CSF enzyme influx from serum outweighs the CNS component.

Acetylcholinesterase in lumbar and ventricular cerebrospinal fluid.

BACKGROUND: Soluble acetylcholinesterase (AChE, E.C. 3.1.1.7.) is released by neurons, glial and meningeal cells into the CSF. AChE activity in cerebrospinal fluid (CSF) is altered in various disorders of the nervous system. The objects of this study are to define a reference range for CSF AChE activity in human lumbar CSF, to prove that the enzyme activity does not depend on the blood/CSF barrier function, and to provide information about AChE in ventricular CSF. In addition, drugs used in neurosurgical care have been examined for their in vitro effects on CSF AChE activity to exclude interference with the test system. METHODS: We tested the AChE activity in 64 lumbar CSF samples collected from a clinically healthy population and in 169 ventricular CSF samples obtained from 90 neurosurgical patients. AChE activity was assayed with our inhibitor-free test procedure. RESULTS: The reference range determined for lumbar CSF AChE activity is 9.2-24.4 nmol/min per ml. Lumbar CSF AChE activity does not correlate with parameters characterising the status of the blood/CSF barrier. Ventricular puncture is only justified for underlying pathology making it impossible to provide reference data for ventricular CSF. Most measurements reveal ventricular enzyme activity below 4 nmol/min per ml. CONCLUSION: The results of this study suggest the utility of lumbar CSF AChE activity as a measure of specific secretory function in enzyme releasing cells of the nervous system.

Sample size determination for testing whether an identified treatment is best.

Laska and Meisner (1989, Biometrics 45, 1139-1151) dealt with the problem of testing whether an identified treatment belonging to a set of k + 1 treatments is better than each of the other k treatments. They calculated sample size tables for k = 2 when using multiple t-tests or Wilcoxon-Mann-Whitney tests, both under normality assumptions. In this paper, we provide sample size formulas as well as tables for sample size determination for k > or = 2 when t-tests under normality or Wilcoxon-Mann-Whitney tests under general distribution assumptions are used.

Clinical performance and periodontal outcome of temporary crowns and fixed partial dentures: A randomized clinical trial.

STATEMENT OF PROBLEM: Different materials (autopolymerizing, dual curing, and light initiated) are used for fabricating provisional restorations during prosthetic treatment. Randomized clinical trials that have evaluated these provisional materials have not been published. PURPOSE: This clinical trial compared the handling, fitting, plaque adherence, gingivitis, color stability, and the subjective assessment of the provisional materials by the patient and the dentist for 2 autopolymerizing (Protemp, Luxatemp), 1 dual-curing (Provipont), and 1 light-initiated (Triad-VLC) material for the manufacturing of temporary crowns and fixed partial dentures. MATERIAL AND METHODS: Thirty subjects in need of 2 similar fixed prosthetic restorations (single crowns ¿20, three-quarter crowns ¿2, connected crowns ¿9, or fixed partial dentures ¿30) were treated with 1 temporary restoration of Protemp II (control) and one randomly selected from Luxatemp, Provipont, or Triad-VLC materials. The mean time of treatment was 37.5 days (minimum 2 days, maximum 156 days). All restorations were manufactured intraorally with a vacuum-formed template. RESULTS: Mechanical and retentive characteristics revealed a high level of clinical reliability. Plaque adherence of the teeth with temporary restorations was significantly increased (P =.0039) compared with the untreated mesial reference teeth. CONCLUSION: The advantageous mechanical properties of the light-curing and dual-curing materials reviewed in dental literature were clinically offset by disadvantages in handling.

Vulval diseases need an interdisciplinary approach.

BACKGROUND: Vulval diseases are common, but their frequency and importance are often underestimated. OBJECTIVE: The study intended to evaluate the number of patients with vulval diseases seen in medical practice. Furthermore, the acceptance of an interdisciplinary vulval disease clinic, managed by a dermatologist in cooperation with a gynaecologist and a psychologist, was evaluated. METHODS: In April and Mai 1998, a mailing survey of all gynaecologists (n = 239), general practitioners (n = 244) and dermatologists (n = 96) in Thuringia, Germany, containing 7 questions concerning patients with vulval diseases was performed. RESULTS: 49% (n = 286) of the questionnaires were returned. On average, 97% of the physicians regularly treated females with genital diseases. The most common diseases mentioned by all specialities were local fungal and bacterial infections. The further ranking of diagnosis was different between the specialities. It was estimated that 83% of patients with chronic disorders would develop additional psychological problems. The necessity of an interdisciplinary vulval disease clinic in Thuringia was stated by 71% of the interviewed physicians. 76% of the gynaecologists and 75% of the general practitioners welcomed the introduction of the clinic. Interestingly, only 51% of the dermatologists felt that a vulval disease clinic was necessary. CONCLUSION: The majority of the physicians in Thuringia welcomed an interdisciplinary vulval disease clinic to improve the conditions for women suffering from genital diseases.

Plasma and buffy coat concentration of 8-methoxypsoralen in patients treated with extracorporeal photopheresis.

Recently, a new therapy involving an extracorporal activation of orally administered 8-methoxypsoralen (8-MOP), photosensitizing furocoumarin, is established for the treatment of different skin diseases, extracorporeal photopheresis (ECP). The pharmacokinetic profile of 8-MOP has been pursued as part of a clinical study which should assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. The enormous intra-individual variations proofed for plasma as well as buffy coat concentration are unfavourable for oral 8-MOP therapy. Therefore, the introduction of liquid 8-MOP formulation that allows the direct administration of the drug in to the treatment bag of the ECP device is challenging.

Nephron sparing surgery for renal cell carcinoma 4 cm. or less in diameter: indicated or under treated?

PURPOSE: Although radical nephrectomy is the standard treatment for localized unilateral renal cell carcinoma with a normal contralateral kidney, there is ongoing interest in the use of nephron sparing surgery or partial nephrectomy in such cases. The extent of radical surgery in such cases has also been reconsidered in view of the uncertainty regarding the malignant or benign nature. MATERIALS AND METHODS: Of 14,793 autopsies in Jena from 1985 until 1995 there were 260 renal cell carcinomas. Of the 260 renal cell carcinomas the diameter was 40 mm. or less in 104. These 104 tumors were divided into group 1-20 mm. or less (33 cases), group 2-21 to 30 mm. (28) and group 3-31 to 40 mm. (43). RESULTS: Grade 1 renal cell carcinomas decreased in frequency with increasing tumor diameter, while an opposite result was noted for grade 3. Lymph node and distant metastases were well correlated with tumor size. With an increase in tumor size the frequency of venous involvement increased as well. Significantly more multifocal malignant renal cell carcinomas were seen in tumors between 21 and 40 mm. compared to those 20 mm. or less in diameter. CONCLUSIONS: The metastatic potential and biology of these small nodules are not yet known. To lower the risk of local recurrence the results of our study suggest that nephron sparing surgery might be advisable in patients with renal cell carcinoma 20 mm. or less in diameter.

Identification of the stimulated hemiretinae using a reduced number of PVEP trials.

Left and right hemifield pattern-reversal visual evoked potentials (PVEP) at P100 latency are characterised by typical field distributions of potential and the spectral parameter instantaneous frequency (IF). Both parameters can be utilised for the correct identification of the stimulated hemiretina in healthy volunteers (Hoffmann, K. et al. Electroenceph. clin. Neurophysiol., 100, 1996: 569-578). The aim of this study was the investigation of the robustness of instantaneous frequency for reduced numbers of averages. Hemifield PVEP of 15 volunteers (20 channel records) were analysed. The number of averages was reduced step-by-step (64-32-16-8-4-1). For each average, the time of P100 latency was determined by the Global field power maximum between 90 and 125 ms. The stimulated hemifield was identified using the potential or instantaneous frequency values at the occipital electrode positions O1 and O2: by maximal potential and instantaneous frequency on the stimulus-contralateral side. In summary, by reduced numbers of averages (as well as by single trials) the stimulated hemiretina was correctly identified more frequently on the basis of instantaneous frequency than of potential distribution. A number of 8 averages seems to be sufficient for the correct identification of the stimulus condition. Consequently, for the identification of left and right hemifield stimulations the recording time could be reduced immensely. Instantaneous frequency is suggested as an additional and robust parameter for the selective averaging of artefact-free trials during the recording of hemifield PVEP.

Drug monitoring of orally administered 8-methoxypsoralen in patients treated with extracorporeal photopheresis.

Recently extracorporeal photopheresis (ECP), a new therapy involving extracorporeal activation of orally administered 8-methoxypsoralen (8-MOP), has been established for the treatment of different skin diseases. The pharmacokinetic profile of 8-MOP has been pursued in a clinical study which aimed to assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. However, the enormous intraindividual variations in plasma as well as buffy coat concentrations affect the efficacy of oral 8-MOP therapy. Therefore, the introduction of a liquid 8-MOP formulation enabling the direct administration of the drug into the treatment bag of the ECP device is challenging.

Measurements of urinary prostaglandins in young ovulatory women during the menstrual cycle and in postmenopausal women.

The purpose of the present work was to study the prostaglandin excretion in young nonpregnant ovulatory women during the menstrual cycle on the one hand and in postmenopausal women on the other hand and to investigate the influence of female sex hormones (estradiol, progesterone) on urinary prostanoid excretion. Urinary excretion rates of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and their metabolites PGE-M (11 alpha-hydroxy-9, 15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid), 2,3-dinor-6-keto-PGF1 alpha, 2,3-dinor-TxB2 and 11-dehydro-TxB2 were determined by gas chromatography-triple stage quadrupole mass spectrometry (GC/MS/MS) in 41 young non-pregnant women during the follicular phase and during the luteal phase and in 23 postmenopausal women. Excretion rates of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. In contrast to the young ovulatory women, PGE2 and TxB2 were significantly higher in postmenopausal women. Concerning the other prostaglandins significant differences between these groups of women did not exist. Although serum levels of estradiol and progesterone were different in young and postmenopausal women, sex hormones have not been shown to correlate with prostaglandins. Our data do not suggest sex hormones to be responsible for the difference in the prostaglandin excretion in women of reproductive age and in women in the menopause. Further systematic investigations into age dependency of prostaglandin excretion in women are necessary.

Intra-individual variability of caffeine elimination in healthy subjects.

Caffeine is a popular test substance for assessing the activity of hepatic drug metabolizing enzymes in vivo and in vitro. A correct estimation of the relative magnitudes of intra-individual and inter-individual variations in caffeine elimination is significant for the use of the elimination parameter of caffeine to characterize the biotransformation capacity of a specific form of cytochrome P-450 (1AII) in vivo. The purpose of this study is to demonstrate the magnitudes of fluctuation of caffeine-clearance and half-life as well as inter- and intra-individual comparison in 12 healthy male subjects. Compared to the high reproducibility of caffeine decay curves in each healthy male, caffeine elimination varied more extensively between subjects. The distribution of variance amounted to: intra-individual 21.4%, inter-individual 78.6%. The knowledge of variance provided precise evidence of the sample size, which is necessary to prove previously defined differences.

Collagen peptidase and type III procollagen peptide serum levels in chronic liver diseases.

The concentration of the N-terminal peptide of procollagen III and the activity of collagen peptidase (PZ-peptidase) were measured in sera from 92 patients with chronic liver disease. In patients with liver cirrhosis and chronic hepatitis with transformation of liver structure, high values were found for both variables compared with hepatoses and chronic hepatitis without transformation. The concentration of procollagen III peptide and the activity of collagen peptidase in serum increased with increasing degrees of fibrosis and, even more markedly, with increasing degrees of mesenchymal activity in the liver.

Virulence of Escherichia coli strains in relation to their hemolysin formation, mannose-resistant hemagglutination, hydroxamate production, K 1-antigen and the plasmid profile in patients with chronic pyelonephritis.

Microorganisms initiating infections of the kidneys and the upper urinary tract are characterized by specific properties. In 96 patients with non-obstructive chronic pyelonephritis, Escherichia coli strains were isolated and their virulence properties studied. Most frequently hemolysin formation and mannose-resistant hemagglutination (n = 39/40%), less frequently the ability to produce hydroxamate/aerobactin (n = 18/19%) and the K 1-antigen (n = 13/14%) were detected. In 34 E. coli strains (35%) two and more virulence factors were found. A statistically significant correlation exists between mannose-resistant hemagglutination (evidence of P- and F7-F14 fimbriae) and hemolysin formation on the one hand and hydroxamate production and K 1-antigen on the other (confidence intervals are 0.56-0.75 and 0.75-0.89, respectively). Disease activity and pathogenicity of E. coli strains showed a statistically significant association (chi 2-value, DF 1: hemolysin 29.5, mannose-resistant hemagglutination 17.1, K 1-antigen 4.8, hydroxamate 0.5). The analysis of the plasmid profile yielded species in molecular weight range from 0-170 Md. A correlation between single virulence features and certain plasmid combinations failed to be demonstrated. The results revealed a close connection between certain virulence properties of E. coli strains and a specific uropathogenicity. The clinical significance of this observation should be further elucidated.