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SummarySetting the reference range for thyrotropin (TSH) remains a matter of ongoing controversy. Patients, methods: We used an indirect method to determine the TSH reference range post hoc in a large sample. A total of 399 well characterised subjects showing no evidence of thyroid dysfunction were selected for definition of the TSH reference limits according to the method of Katayev et al. To this end, the cumulative frequency was plotted against the individual logarithmic TSH values. Reference limits were calculated by extrapolating the middle linear part of the regression line to obtain the cut-offs for the 95% confidence interval. We also examined biological variation in a sample of 65 subjects with repeat measurements to establish reference change values (RCVs). Results: Based on these, the reference interval obtained by the novel technique was in close agreement with the conventionally established limits, but differed significantly from earlier recommendations. Discussion: Following unverified recommendations could result in a portion of patients with subclinical thyroid dysfunctions being missed, an important consideration in a setting with a high prevalence of thyroid autonomy. Conclusion: Indirect post hoc verification of reference intervals from a large retrospective sample is a modern approach that gives plausible results. The method seems particularly useful to assess the adequacy and performance of reference limits reported or established by others in a particular setting. The present data should encourage re-evaluation of reference systems on a broader scale.

Several in vivo and in vitro studies on the stereoselective potency of isoflurane enantiomers suggest beneficial effects of the (+)-(S)-enantiomer. In order to detect possible differences in the pharmacokinetics of isoflurane enantiomers, a clinical study of 41 patients undergoing general anesthesia maintained with racemic isoflurane was performed. The isoflurane enantiomers were analyzed in blood samples drawn before induction, at cessation (day 0), and up to eight days after isoflurane anesthesia (day 1–8). A multipurpose sampler (Gerstel® MPS) was used for the headspace gas chromatography-mass spectrometry (GC/MS) analysis, and it was combined with a cold injection system (Gerstel® CIS 3) for coldtrapping, enrichment, and focusing of the analyte. The enantiomer separation was achieved by using a capillary column coated with octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E®) dissolved in the polysiloxane PS 255. Detection was done in the selected ion monitoring mode with ions m/z 117 and m/z 149. An enrichment of (+)-(S)-isoflurane in all blood samples drawn after anesthesia was found. The highest enantiomer bias, up to 52–54% (+)-(S)-isoflurane as compared to 50% for the racemate, was observed on day 2 for most of the patients. Furthermore, quantification of isoflurane in blood samples of five patients was done by enantiomer labeling, employing enantiomerically pure (+)-(S)-isoflurane as internal standard. The isoflurane concentration decreased rapidly from 383 nmol/ml to 0.6 nmol/ml (mean values) eight days after anesthesia. The present study shows differences in the pharmacokinetics of isoflurane enantiomers in man. However, it is not possible to distinguish between enantioselective distribution and enantioselective metabolism, if any. Chirality 11:206–211, 1999. © 1999 Wiley-Liss, Inc.

Purpose In XeCl-Excimer laser angioplasty, unintended and possibly harmful interaction of the UV-laser light and the contrast media may occur due to the high concentration of contrast medium proximal to the occlusion or subtotal stenosis. Methods One ml of three nonionic monomeric contrast agents (iopromide, iomeprol, iopamidol), one nonionic dimeric (jotrolane), and one ionic monomeric (amidotrizoate) X-ray contrast agent were irradiated with a XeCl excimer laser (lambda = 308 nm, pulse duration 120 ns, 50 Hz) using a 9 French multifiber catheter (12 sectors). Up to 20,000 pulses (106 J) were applied. Using high performance liquid chromatography the amount of liberated iodide as well as the fraction of unchanged contrast media were measured. Cytotoxicity of the photoproducts was tested in a colony formation assay of human skin fibroblasts. The contrast agents were irradiated with 2000 pulses/ml (5.3 mJ/pulse; 10.6 J) and then added to the cell cultures for a period of three hours in a concentration of 10%. Results Excimer laser irradiation induced iodide liberation of up to 3.3 mg iodide/ml. Up to 19% of the contrast agents changed their original molecular structure. Incubation of irradiated contrast agents resulted in a significantly decreased potential for colony formation (p values ranging from 0.0044 to 0.0102) with significantly higher toxicity of amidotrizoate and iomeprol in comparison to iopromide, iotrolan, and iopamidol. Discussion Due to the cytotoxic photoproducts and the high level of liberated iodide, it is recommended to flush the artery with physiological saline solution before applying a pulsed excimer laser in human arterial obstructions in order to reduce the contrast agent concentration at the site of irradiation.

Patientennahe Glukosemessungen sind fur eine optimale Stoffwechseleinstellung von Menschen mit Diabetes notwendig und essenzieller Bestandteil der Diabetesbehandlung gemas den evidenzbasierten Leitlinien der Deutschen Diabetes-Gesellschaft (DDG) [1]. Man unterscheidet eine patientennahe quantitative Blutglukosebestimmung durch medizinisches Personal, die u.a. der Qualitatssicherung nach den Richtlinien der Bundesarztekammer (Richtlinie der Bundesarztekammer zur Qualitatssicherung laboratoriums-medizinischer Untersuchungen, RiliBAK) unterliegt, von einer Selbsttestung der Betroffenen bzw. durch deren Angehorige, der Blutglukoseselbstkontrolle (BGSK), fur die keine gesetzlich geregelte Qualitatskontrolle erforderlich ist. Die klinischen Anforderungen an die BGSK-Testsysteme und deren erfolgreicher Einsatz im Laienalltag haben auch die technologische Entwicklung von POCT-Systemen fur die Glukosemessung wesentlich mitgepragt. Im Vergleich zur Situation vor etwa 10Jahren sind die Gerate heute kleiner, schneller, einfacher zu bedienen und interferenzunabhangiger und kommen mit immer geringeren kapillar entnommenen Blutmengen aus (▸ Kap. 6).

Isoflurane is a chiral volatile anaesthetic, routinely administered as racemate. It has a low metabolic rate and is mostly eliminated via respiration. In blood samples, S(+) enantiomers are found in greater proportion in the days immediately after administration of isoflurane racemate whereas the ratio in breath samples is unknown.Breath and blood samples were drawn immediately after recovery and daily up to 19 days after operation from patients undergoing anaesthesia with isoflurane racemate. The percentage of isoflurane enantiomer was determined by gas chromatography mass spectrometry in blood and thermodesorption gas chromatography mass spectrometry in breath samples.In breath samples, there were significant differences in S(+) enantiomers at all time points compared to the racemate. During the early postoperative phase, the percentage of S(+) enantiomers were significantly enhanced whereas 5 days after surgery predominantly R(-) enantiomers (50.41%) were detected in the breath samples. Also in blood samples a statistical significant accumulation of the S(+) enantiomer was noted between days 1 and 5 compared to isoflurane racemate blood control. S(+) enantiomers were significantly higher in blood compared to breath samples and was most evident on the third day after surgery (51.43%).During the first days after application of isoflurane racemate, the percentage of S(+) enantiomers are higher in breath and blood samples of patients. We suggest that resorption and/or redistribution of enantiomers are responsible for the different kinetics of isoflurane enantiomers.

In addition to sc and visceral fat deposits, muscle has been shown to contain relevant amounts of lipids whose breakdown is subject to hormonal regulation. The aim of the present study was to determine insulin dose-response characteristics of systemic, sc adipose tissue and muscle lipolysis in humans. We used a combination of isotopic (primed continuous infusion of [d5]glycerol) and microdialysis techniques (catheters placed in the anterior tibial muscle and sc abdominal adipose tissue) during a three-step hyperinsulinemic-euglycemic clamp (insulin infusion, 0.1, 0.25, 1.0 mU/kg x min) in 13 lean, healthy volunteers. The glycerol rate of appearance was used as the index for systemic lipolysis; interstitial glycerol concentrations were used as the index for muscle and sc adipose tissue lipolysis. The insulin concentrations resulting in a half-maximal suppression (EC50) of systemic lipolysis, adipose tissue, and muscle lipolysis were 51, 68, and 44 pmol/L, respectively (between one another, P0.001). For each compartment there were significant correlations between the EC50 and the insulin sensitivity index for glucose disposal (r0.67; P0.05). However, lipolysis (as percent of baseline) was similar during the first two insulin infusion steps, but was significantly lower in adipose (22+/-2%) than in muscle (53+/-4%; P0.001) during step 3. Although we have no direct measurement of interstitial insulin concentrations, we conclude that based on the EC50 values, muscle is more sensitive with respect to the net effect of circulating insulin (transendothelial transport plus intracellular action) on lipolysis than sc adipose tissue in terms of exerting its full suppression within the physiological insulin range. This could be important in muscle for switching from preferential utilization of free fatty acids to glucose in the postprandial state. Inadequate suppression of im lipolysis resulting in excessive local availability of free fatty acids may represent a novel mechanism contributing to the pathogenesis of impaired glucose disposal, i.e. insulin resistance, in muscle.

In XeCl-Excimer laser angioplasty, unintended and possibly harmful interaction of the UV-laser light and the contrast media may occur due to the high concentration of contrast medium proximal to the occlusion or subtotal stenosis.One ml of three nonionic monomeric contrast agents (iopromide, iomeprol, iopamidol), one nonionic dimeric (jotrolane), and one ionic monomeric (amidotrizoate) X-ray contrast agent were irradiated with a XeCl excimer laser (lambda = 308 nm, pulse duration 120 ns, 50 Hz) using a 9 French multifiber catheter (12 sectors). Up to 20,000 pulses (106 J) were applied. Using high performance liquid chromatography the amount of liberated iodide as well as the fraction of unchanged contrast media were measured. Cytotoxicity of the photoproducts was tested in a colony formation assay of human skin fibroblasts. The contrast agents were irradiated with 2000 pulses/ml (5.3 mJ/pulse; 10.6 J) and then added to the cell cultures for a period of three hours in a concentration of 10%.Excimer laser irradiation induced iodide liberation of up to 3.3 mg iodide/ml. Up to 19% of the contrast agents changed their original molecular structure. Incubation of irradiated contrast agents resulted in a significantly decreased potential for colony formation (p values ranging from 0.0044 to 0.0102) with significantly higher toxicity of amidotrizoate and iomeprol in comparison to iopromide, iotrolan, and iopamidol.Due to the cytotoxic photoproducts and the high level of liberated iodide, it is recommended to flush the artery with physiological saline solution before applying a pulsed excimer laser in human arterial obstructions in order to reduce the contrast agent concentration at the site of irradiation.

Between 1973 and 1987 a total of 1698 patients with fractures of the proximal femur were operatively treated at the surgical accident and emergency department of the Städtische Krankenanstalten Krefeld. The most commonly observed fracture in the high age group (mean: 81.4 years) was that of the subcapital femoral neck (n = 901). A total hip replacement (n = 648) was commonly indicated - followed by a hemiarthroplasty (n = 114) and 130 AO plate (n = 70). Fractures of the femoral neck in young patients were treated with a cancellous screw in order to preserve the femoral head (n = 69). The majority of pertrochanteric fractures (n = 603) were stabilized with 130 degrees AO plates (n = 520) and most of the subtrochanteric fractures (n = 194) were treated either with an angle plate (n = 130) or with a 95 degrees AO plate (n = 64). In principle early internal fixation followed by immediate mobilization was the aim in all patients (68% of patients were operated on within three days of admission). Sufficient stability was achieved using internal fixation to allow full weight bearing in 76% of the injuries, or partial weight bearing in 21% postoperatively. The paper shows that the patients need spend less time in the hospital (60% stayed less than three weeks on the ward, 80% were discharged within four weeks) and that the mortality in this study was reduced to 10.1%. Complications such as fracture of the implant (0.5%) and dislocation (0.9%) were described. The rate of bone infection amounted to 0.9% of all operations.

Between 1973 and 1990 a total of 2012 patients with fractures of the proximal femur were operatively treated at the surgical accident and emergency department of the Städtische Krankenanstalten Krefeld. The most commonly observed fracture in the high age group (mean: 81.2 years) was that of subcapital femoral neck (n = 1067). A total hip replacement (TEP n = 768) or a hemiarthroplasty (n = 135) was indicated in 85% of the cases. All patients in which a head preserving internal fixation was possible, were normally treated as an emergency with a cancellous screw (n = 81) or stabilized with 130 grade angled plate (n = 83). Pertrochanteric femur fractures (n = 715) were mainly stabilized with 130 grade angled plates (n = 605). In subtrochanteric femur fractures (n = 230) a 130 grade angled plate (n = 155) or a 95 grade condylar plate (n = 75) was used. In principle early internal fixation followed by immediate mobilization was the aim in all patients (68% of patients were operated on within three days of admission). Sufficient stability was achieved using internal fixation to allow full weight bearing in 76% of the injures, or partial weight bearing in 21% postoperatively. The paper shows that the patients need spend less time in the hospital (60% stayed less than three weeks on the ward, 80% were discharged within four weeks) and that the mortality in this study was reduced to 10.1% in comparison with formerly studies. Complications such as fracture of the implant (0.5%) and dislocation (0.9%) were described. The rate of bone infection amounted to 0.9% of all operations.

Background and objective: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics. Methods: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry. Results: At all time points, there was a statistically significant accumulation of the S (+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations. Conclusions: We suggest that a slower association and dissociation rate is responsible for the S (+) enrichment.

In den Jahren von 1970–1977 wurden an unserer Klinik 518 altere Patienten mit Frakturen des proximalen Femurendes operativ versorgt (397 Frauen, 121 Manner). Die Altersverteilung zeigt Abb. 36. Das Durchschnittsalter betrug 74,5 Jahre, die Aufteilung der Frakturen zeigt Tabelle 26.

Bei 30 von verschiedenen Operateuren durchgefuhrten groBen Osteosynthesen wurde die Strahlenbelastung (Ganzkorper- und Teilkorperbestrahlung) mittels Fotoluminiscenzdosimetern gemeBen. Die ermittelten Belastungswerte fur das Personal sind so geringfugig, daB sie vernachlaBigt werden konnen. Ebenfalls die Strahlenbelastung des Operateurs bezuglich der Gonaden. Kritische Werte dagegen bei der Strahlenbelastung der Augen und Hande werden bei langeren Einschaltzeiten bei haufigen Osteosynthesen erreicht. Aus diesem Grunde muB ausdrucklich vor zu haufiger Anwendung und Einschaltung auch des Bildverstarkers gewarnt werden.