Surgical resection of thymoma still represents the first choice of treatment.

OBJECTIVE: The aim of this study was to analyze the clinicopathological factors, treatment strategies and survival rates after surgical resection of thymoma. METHODS: Between 12/1997 and 5/2010, 42 patients underwent surgical resection of the thymus. The presence of a thymoma was determined by histological examination in 23 patients, while patients with hyperplasia of the thymus (n = 19) were excluded from further analysis. RESULTS: Myasthenia gravis coexisted in 9/23 (39.1%) patients. Thymomas were classified according to the Masaoka staging system (I: n = 6 [26.1%], IIa: n = 7 [30.4%], IIb: n = 2 [8.7%], III: n = 1 [4.4%], IVa: n = 7 [30.4%]) and the WHO histological classification (A: n = 4 [17.4%], AB: n = 5 [21.7%], B1: n = 1 [4.4%], B2: n = 8 [34.8%], B3: n = 3 [13%], C: n = 2 [8.7%]). Recurrence of thymoma was documented in three (13%) patients. After a mean follow-up of 58.4 months, 21 (91.3%) patients are alive. The overall survival rate was 95% and 87.8%, at 2 and 5 years, respectively. The disease-free interval at 5 years was 85% for the 17 (73.9%) patients with complete resection. CONCLUSIONS: Surgical resection of thymoma is the preferred treatment, because it is safe and effective with a low rate of recurrence and a good long-term survival. Advanced and invasive thymomas require a multimodal approach for better local tumor control and further improvement of prognosis.

Optimal secondary coil design for inductive powering of the Artificial Accommodation System.

Age-related ailments like presbyopia and cataract are increasing concerns in the aging society. Both go along with a loss of ability to accommodate. A new approach to restore the patients' ability to accommodate is the Artificial Accommodation System. This micro mechatronic system will be implanted into the capsular bag to replace the human crystalline lens. Depending on the patients' actual need for accommodation, the Artificial Accommodation System autonomously adapts the refractive power of its integrated optical element in a way that the projection on the patients' retina results in a sharp image. As the Artificial Accommodation System is an active implant, its subsystems have to be supplied with electrical energy. Evolving technologies, like energy harvesting, which can potentially be used to power an implant like the Artificial Accommodation System are at the current state of art not sufficient to power the Artificial Accommodation System autonomously [1]. In the near future, therefore an inductive power supply system will be developed which includes an energy storage to power the Artificial Accommodation System autonomously over a period of 24 h and can be recharged wirelessly. This Paper describes a new possibility to optimize the secondary coil design in a solely analytical way, based on a new figure of merit. Within this paper the developed figure of merit is applied to optimize the secondary coil design for the Artificial Accommodation System.

[Energy and memory efficient calculation of the accommodation demand in the artificial accommodation system]. / Energie- und speichereffiziente Berechnung des Akkommodationsbedarfs im Künstlichen Akkommodationssystem.

Presbyopia and cataract are gaining more and more importance in the ageing society. Both age-related complaints are accompanied with a loss of the eye's ability to accommodate. A new approach to restore accommodation is the Artificial Accommodation System, an autonomous micro system, which will be implanted into the capsular bag instead of a rigid intraocular lens. The Artificial Accommodation System will, depending on the actual demand for accommodation, autonomously adapt the refractive power of its integrated optical element. One possibility to measure the demand for accommodation non-intrusively is to analyse eye movements. We present an efficient algorithm, based on the CORDIC technique, to calculate the demand for accommodation from magnetic field sensor data. It can be shown that specialised algorithms significantly shorten calculation time without violating precision requirements. Additionally, a communication strategy for the wireless exchange of sensor data between the implants of the left and right eye is introduced. The strategy allows for a one-sided calculation of the demand for accommodation, resulting in an overall reduction of calculation time by 50 %. The presented methods enable autonomous microsystems, such as the Artificial Accommodation System, to save significant amounts of energy, leading to extended autonomous run-times.

On-line production of ultrapure substitution fluid reduces TNF-alpha- and IL-6 release in patients on hemodiafiltration therapy.

On-line hemodiafiltration (HDF) has been introduced into clinical practice in the last few years. The most important technical and regulatory challenges were the safety and microbiological quality of ultrafiltrated substitution/replacement fluid. The application of ultrafilters in a different technical arrangement in the fluid path based on polysulfone or polyamide membranes should prevent patient contact with endotoxins and other pyrogenic or bacteria-derived substances. After resolving these problems and providing clinically safe and technically robust product solutions, increasing numbers of patients have been treated, especially those with severe clinical conditions, e.g., diabetes, hypo- or hypertension. The benefit for patients was brought about by the increase of substitution rate in hemodiafiltration and enhancing convective mass transfer. The impact of highly convective therapy modes on the state of immunomodulation towards the syndrome of microinflammation has not been investigated in a systematic prospective manner. In this study, 8 patients undergoing bag-HDF treatment with lactate buffered solution were investigated before on-line HDF treatment with commercially available whole blood stimulation assays testing for TNF-alpha and IL-6 release. Both assays are based on phytohemagglutinine (for TNF) and lipo-polysaccharide stimulation (for IL-6). Thereafter the patients were switched to on-line production of substitution fluid. After a wash-out period of 2 sessions the whole blood stimulation assays were applied to the same patients. The Wilcoxon test (for paired analysis) was done, revealing a statistically significant lower release of proinflammtory cytokines from patients' blood upon stimulation with PHA or LPS. The reduction of IL-6 and TNF concentration and release capacity in whole blood may be attributed to the use of high quality ultrapure substitution fluid and dialysate in on-line treatment instead of lactate buffer bag solution. These results indicate that not only an increase of convective mass transfer by higher volume exchange, but also a decrease in unspecific activation of immunocompetent cells may have advantages for HDF-treated patients.

The measurement of cytokine production capacity during dialysis--a new dynamic method for the evaluation of biocompatibility?

The activation of monocytes and other immunocompetent cells during hemodialysis can be attributed to their contact with immunogenic structures such as membranes, blood lines, and endotoxins. The simple measurement of cytokines in blood cannot completely describe the whole dimension of this event. Stimulation of monocytes and other immunocompetent cells in whole blood with lipopolysaccharides (LPS) for IL-6 and phytohemagglutinine (PHA) for TNF at the start and end of dialysis may make it possible to better analyze cellular response during dialysis. Ten healthy volunteers and 10 patients suffering from chronic renal failure were tested with the commercial whole-blood stimulation assays "Dynamix"-IL-6-DIA and -TNF-alpha-DIA (Biosource Diagnostics, Ratingen, Germany). Then 24 patients undergoing hemodialysis with hemophane (n=12) and polyamide (n=12) membranes were examined before and after dialysis treatment. The unpaired Wilcoxon t- test was used for statistical analysis. Healthy volunteers and patients with chronic renal failure showed no statistical differences in concentrations of TNF-alpha and IL-6 before or after whole blood stimulation (WBS). In comparison to patients with chronic renal failure, pre-WBS concentrations of both cytokines (p<0.034) were increased in patients of each membrane group before dialysis. After whole blood stimulation, no differences were observed. At the end of dialysis treatment, the pre- and post-WBS IL-6 values were both significantly higher in the hemophane group (p=0.049 and p=0.0038, respectively) TNF-alpha concentrations were unchanged. No significant differences in the polyamide group were found between the start and end of treatment for either cytokine. A comparison of these membrane groups showed that only the pre-WBS IL-6 concentration in the hemophane group was elevated (p=0.022) after dialysis. In conclusion, the presence of uremia alone could not influence the cytokine production and release capacity. In our patients, dialysis elevated pre-WBS concentrations of TNF-alpha and IL-6, and increased IL-6 release from immunocompetent cells after whole blood stimulation in the hemophane group. The use of polyamide membranes decreased the action of monocytes and other immunocompetent cells, but could not completely prevent this phenomenon. The whole blood stimulation assays for measurement of TNF-alpha and IL-6 may represent a new, dynamic method for evaluating biocompatibility.

Development of a stable isotope dilution assay for the quantification of 5-methyl-(E)-2-hepten-4-one: application to hazelnut oils and hazelnuts.

A stable isotope dilution assay was developed for the quantitation of the hazelnut odorant 5-methyl-(E)-2-hepten-4-one by mass chromatography using synthesized [(2)H](2)-5-methyl-(E)-2-hepten-4-one as the internal standard. Application of the method on two batches of commercial hazelnut oils, processed from either roasted or unroasted nuts, revealed 6.4 microg 5-methyl-(E)-2-hepten-4-one per kg of unroasted oil whereas 315.8 microg per kg was determined in the roasted nut oil. The about 50-fold higher amount of 5-methyl-(E)-2-hepten-4-one in roasted hazelnut oil suggested the necessity of a thermal treatment to generate the flavor compound. Pan frying of raw hazelnuts (9 to 15 min) or boiling of the crushed nut material for 1 h in water led to an increase of 5-methyl-(E)-2-hepten-4-one by factors of 600 and 800, respectively, thereby corroborating that the major part of the nut flavorant is formed during heat treatment from a yet unknown precursor in hazelnuts.

Presence of factor-VII and -XIII activity in ultrafiltrate during hemofiltration.

UNLABELLED: Bleeding complications during renal replacement therapies can be attributed to coagulation system and platelet function alterations in uremia, and the application of heparin in extracorporeal circulation. Small protein losses during hemofiltration are always described, however the high molecular weight of coagulation factors should significantly prevent their removal during hemofiltration. To exclude degradation of coagulation factors under conditions of spontaneous ultrafiltration, the hemofiltrate of 40 patients with acute renal failure (treated with continuous veno-venous hemofiltration, CVVH) was sampled from the filtrate line after 1 h from the beginning of treatment and in 5 patients also after 12 and 24 h. Samples were investigated with human factor deficient plasma (VII, X, XI, XII) from donors with a congenital deficiency and with human plasma depleted of factor V, VIII, IX, and protein S and C. Factor XIII was detected photometrically. Subsequently the presence of factor- XIII and -VII activity was investigated in plasma and hemofiltrate from 16 patients treated with intermittent hemofiltration before (plasma) and after (plasma, hemofiltrate) therapy. These patients also suffered from acute renal failure and needed renal replacement therapies. Quality control was carried out with a buffer solution (<1% activity in the assays according to recommended protocols). RESULTS: Factor-V, -VIII, -IX, -X, -XI, and -XII activity, and protein C and S could not be detected in the hemofiltrate from continuous hemofiltration. Factor-VII and -XIII activity was present in the hemofiltrate (mean activity in CVVH: 1.93% for factor VII and 6.9% for factor XIII, mean activity in intermittent hemofiltration: <1% for factor-VII and 7.3% for factor-XIII). Three were no significant differences (Student's t-test) in plasma activity before and after intermittent hemofiltration of factor VII (44 vs. 47%, p = 0.39) and factor XIII (44 vs. 52%, p = 0.24). The presence of factor-VII and -XIII activity in the hemofiltrate cannot influence plasma activities in intermittent hemofiltration. Rapid new synthesis and short half-life should neutralize these effects. Elimination of coagulation factor-XIII activity should be excluded by the next generation of highly permeable membranes and on-line hemodiafiltration.

Which organic acids does hemofiltrate contain in the presence of acute renal failure?

It is not generally possible to measure most organic acids in the serum of critically ill patients, due to rapid metabolism and methodological problems. Only the regular measurement of lactic acid and the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate, AKBR) have been introduced in clinical practice, but these parameters can represent only a part of the disturbed metabolism. In pediatric patients, a chromatographical urine analysis has been established for detection of inborn errors of metabolism, which allows the determination of more than 50 organic acids simultaneously (gas chromatographic (GC) analysis in combination with mass spectrometry (MS)]. In continuous treatment of acute renal failure, hemofiltrate is always available, but it contains only low protein concentrations and after the filtration process, metabolism is rapidly stopped. The sieving coefficient of lactic acid is nearly one in hemofiltration. The aim of our study was to compare results of the regular and CG/MS methods in blood and hemofiltrate for lactic acid, and to find other organic acids of possible clinical importance. We investigated serum (lactic acid) and hemofiltrate of 40 critically ill patitens, similar to the urine analysis method for infants. All patients suffered from acute renal failure and were treated by continuous veno-venous hemofiltration (CVVH). The conditions of treatment were standardized (spontaneous ultrafiltration in the first hour), and the material (blood/hemofiltrate) was taken one hour after the beginning of extracorporeal circulation. Statistical methods included correlation analysis, nonparametric ANOVA with Wilcoxon scores (ranks of data), and stepwise discriminant analysis. Regular and GC/MS methods in hemofiltrate showed a good correlation for lactic acid. The best correlation with lactic acid was found for 4-hydroxy-phenyllactic acid (n=20, r=0.866), 2-hydroxy-valeric acid (n=22, r=0.7491) and 2-hydroxybutyric acid (n=32, r=0.5148). Age, sex, diagnosis, and APACHE II score play a subordinate role, but the presence of glyceric and citric acid possibly have prognostic importance [nonparimetric ANOVA with Wilcoxon scores (ranks of data)], as does the combination of 3-hydroxypropionic acid, glyceric acid, and threonic-acid-4-lacton (stepwise discriminant analysis). It can be concluded that in acute renal failure, the measurement of lactic acid and AKBR can reflect only a small part of disturbed metabolism. Hemofiltrate can be a useful medium in describing metabolic processes in critically ill patients with acute renal failure. Some inherited metabolic diseases in infants (phenylketonuria, maple syrup disease) and ketoacidosis show similar metabolic modifications.

Which amino-acids do serum and hemofiltrate of critically ill patients with acute renal failure contain?

The removal of amino acids during continuous renal replacement therapies induces clinical problems. Previous studies on animals have shown nephroprotective (glycine, alanine) or negative effects (lysine) on renal function in occurrence of acute renal failure. Disturbed metabolism in acute renal failure needs adequate parenteral nutrition. On the other hand, experience with continuous renal replacement therapies of metabolic crises in inborn errors of metabolism indicate a good control of disturbed amino acid metabolism. The aim of our study was to find amino acids, that might play an important role in the pathogenesis, prognosis and detection of acute renal failure and severe illness, so far only estimated by lactic acid. Thirty-three probes (serum and hemofiltrate) were taken from patients, suffering with acute renal failure caused by septic shock, severe pancreatitis and hepatorenal syndrome, one hour after the beginning of extracorporal circulation, the conditions of treatment were standardized. The material was deproteinized and studied by the amino acid analyzer LBK 4251 Apha Plus (Pharmacia, Stockholm, Sweden), while the lactic acid concentration was determined in a standard laboratory. Proline, glycine, alanine, methionine and histidine showed a close relationship to the lactic acid levels, but these amino acids were an essential part of parenteral nutrition. A statistical relationship was also established in (amino acids with amide groups) asparagine, glutamine, citrulline, cystathionine and phosphoethanolamine. The mean values of most of the amino acids were higher than normal, but standard deviations were increased. The presence of these amino acids in hemofiltrate and the good sieving coefficients could mean that the better prognosis of critically ill patients in continuous renal replacement therapies may also be due to continuous control of amino acid levels (especially with amide groups).

Dependence of the 12-methyltridecanal concentration in beef on the age of the animal.

The content of 12-methyltridecanal (12-MT), which contributes greatly to the characteristic aroma of stewed beef, was determined by a stable isotope dilution assay in meat samples from nine bovine animals of different ages. The results, which were related to the amount of phospholipids (PL), indicate that 12-MT content increases with the age of beef, e.g., from 36 micrograms.g(-1) PL in a 4-month-old calf to 810 micrograms.g(-1) PL in an 8-year-old cow. The increase of 12-MT content in PL per month varied between 8.4 and 10.9 micrograms.g(-1) PL (mean: 9.3 +/- 0.78 micrograms.g(-1) PL). Possibly 12-MT content is suitable as an indicator for the estimation of the age of a beef sample.

Quantitative analysis of caffeic and ferulic acids in oatmeal. Comparison of a conventional method with a stable isotope dilution assay.

[13C]Caffeic acid and [13C]ferulic acid were synthesized and then used as internal standards for the determination of these acids (free and esterified) in oatmeal. A comparative study indicated that 84% of the ferulic acid, but only 32% of the caffeic acid, which is more susceptible to oxidation than the former, could be found by a conventional analytical approach.

Chronic recurrent appendicitis. A clinicopathologic study of 47 cases.

As part of a retrospective study 47 appendices from patients with a clinical and morphologic diagnosis of chronic recurrent appendicitis were studied by morphologic and immunohistochemical methods. Appendices with chronic recurrent appendicitis histologically show chronic active inflammation with increased numbers of immunocompetent cells, mostly T lymphocytes and subsequent scarring. In addition, there is an increase in the number of neural cells. Apparently the secretion of neurotropic inflammatory mediators, especially by activated and degranulating eosinophils, leads to a stimulation of nociceptive receptors and thus to the clinical symptoms. The diagnosis of recurrent chronic appendicitis is thus warranted in these cases not only clinically but also on the basis of histologic and immunohistochemical findings.

[Value of bone scintigraphy in secondary (intestinal) hyperparathyroidism]. / Zur Bedeutung der Skelettszintigraphie beim sekundären (intestinalen) Hyperparathyreoidismus.

We report on 4 patients with secondary hyperparathyroidism of intestinal origin presenting a characteristical pattern of distribution, namely focal accumulations of 99mTc-methylene diphosphonate on locations typical of Looser's zones. In accordance with other authors we demonstrate the higher sensitivity of skeletal scintigraphy as compared to radiography which is well known from other disorders of bone. We also refer to the problems of differential diagnosis arising when multiple foci are visible on bone scan.