[Establishing a quality management system according to DIN EN ISO 9001:2000 in an academic radiological department]. / Aufbau eines Qualitätsmanagementsystems nach DIN EN ISO 9001:2000 in einer radiologischen Universitätsklinik.

PURPOSE: Establishing a quality management (QM) system according the guidelines of DIN EN ISO 9001:2000 in an academic radiological department. MATERIALS AND METHODS: To fulfill the requirements of an academic radiological department a quality management system according the guidelines of DIN EN ISO 9001 : 2000 has been established within one year. All important educational, research and patient care issues have been discussed in plenary sessions of all employees of the department twice a week. All core processes of the department have been documented as process instructions and standard operation procedures. RESULTS: Supported by the staff unit "quality assurance" of the university hospital, the QM system has been established during one year. Assisted by all parties of the department, obliging regulations have been established which are well accepted in the daily routine clinical work but also in research and education. The implementation of the QM system caused an additional work load. However, spreading the work load by a consequent responsibility assignment, it could be reduced effectively. CONCLUSION: The implementation of a QM system within the daily routine work of an academic radiological department is feasible. It allows the installation of generally accepted rules which regulate the principal tasks of research and education, and patient care.

[Introduction of a quality management system compliant with DIN EN 9001:2000 in a university department of nuclear medicine]. / Einführung eines Qualitätsmanagementsystems nach DIN EN ISO 9001:2000 in einer universitären nuklearmedizinischen Abteilung.

In 1995, the management of the University Clinic Hamburg-Eppendorf proposed to establish a total quality assurance (QA) system. A revised QA-system has been introduced stepwise in the department of nuclear medicine since 1997, and certification was achieved in accordance with DIN EN ISO 9001:2000 on February 14, 2001. The QA-handbook is divided into two parts. The first part contains operational (diagnostic and therapeutic) procedures in so-called standard operating procedures (SOP). They describe the indication of procedures as well as the competences and time necessary in a standardized manner. Up to now, more than 70 SOPs have been written as a collaborative approach between technicians and physicians during daily clinical routine after analysing and discussing the procedures. Thus, the results were more clearly defined processes and more satisfied employees. The second part consists of general rules and directions concerning the security of work and equipment as well as radiation protection tasks, hygiene etc. as it is required by the law. This part was written predominantly by the management of the department of nuclear-medicine and the QA-coordinator. Detailed information for the patients, documentation of the work-flows as well as the medical report was adopted to the QM-system. Although in the introduction phase of a QA-system a vast amount of time is necessary, some months later a surplus for the clinical workday will become available. The well defined relations of competences and procedures will result in a gain of time, a reduction of costs and a help to ensure the legal demands. Last but not least, the QA-system simply helps to build up confidence and acceptance both by the patients and the referring physicians.

[Do we need a special language in quality management?]. / Brauchen wir eine Fachsprache im Qualitätsmanagement?

For matters outside our everyday experience we need a technical language. Its semantics and syntax must be carefully constituted from basic concepts and conclusions. A specialist language is easy to understand, precise and economical. The terminology of quality management has proved useful--irrespective of the product--on an international and intercultural stage. It is applicable in product- and service-industry as well as in health care. It does not relieve anybody from the pain of getting used to these programs. The specialist terminology paves the way for acting in a technical sense. In this the specialist use of language differs from a political and religious use of language.

[Evaluation of the bioequivalence of two fast-releasing iron(II) sulfate formulations]. / Prüfung der Bioäquivalenz von zwei schnellfreisetzenden Eisen(II)-Sulfat-Formulierungen.

Bioequivalence of a new oral iron formulation (A: FE(II)SO4.H2O, capsule with 100 mg Fe++, Eryfer 100, CAS 7782-63-0) with the standard formulation (B: Fe(II)SO4.H2O, capsule with 50 mg Fe++, Eryfer) was demonstrated after administration of 100 mg Fe++ in a single-dose two-way cross-over design to 16 normal female volunteers. Iron concentrations were monitored from 24 h before (basal) to 24 h post application. The area under concentration difference curve AUC(diff) and the maximal concentration difference Cmax(diff) were calculated subtracting the basal from the time-corresponding postabsorptive concentrations. AUC(diff) (A: 170 nmol/ml. h, B: 168 nmol/ml.h) and Cmax(diff) (A: 23.3 nmol/ml, B: 21.8 nmol/ml) showed but minor differences between formulations. The AUC(diff) and Cmax ratio (A/B) and the corresponding 90% confidence intervals, 102% (74-129%) and 107% (91-123%), were included by the acceptance range of 70-130% as stated in the study protocol. Hence, both formulations were bioequivalent with respect to rate and extent. The ANOVA coefficient of variation of Cmax(diff) was considerably smaller than that of AUC(diff) (26% versus 44%). The characteristics based on the postabsorptive iron increase (post-absorptive concentrations minus concentration preceding immediately application) AUC(pad) (ratio 99% (83-114%) and Cmax(pad) (ratio 104% (95-112%) exhibited smaller ANOVA-CVs (25% and 14%, respectively) as compared with AUC(diff) and Cmax(diff). All these characteristics appeared to be rather normal than log-normal distributed. It was concluded that the study design was selective to demonstrate an adequate bioavailability of iron formulations.

[The infiltrating angiolipoma--a rare soft tissue tumor with a malignant appearance]. / Das infiltrierende Angiolipom--ein seltener Weichgewebstumor mit malignem Erscheinungsbild.

Angiolipomas are rare benign soft tissue tumours that are mostly encapsulated by fibrous tissue. A case of an infiltrating angiolipoma with mixed vascularisation, not surrounded by a capsule, is described. Differentiation between lipoid degenerated fibromas, lipoid histiocytoses and haemangiomas is radiologically possible with an extensive security and enables an adequate choice of the surgical procedure.

[The tracer concept of quality assurance in the hospital--a critical evaluation]. / Das Tracer-Konzept der Qualitätssicherung im Krankenhaus--eine kritische Uberprüfung.

The "tracer concept", on which the introduction of quality assurance measures in Germany according to section 137 GRG is based, are critically confronted with the general test philosophy. It is shown that this tracer methodology does not come up to expectations and should be abandoned. Development and introduction of indicators are recommended that would be more appropriate to attain the target of quality assurance: quality improvement.

Glucoregulatory function of thyroid hormones: evidence for an insulin-independent effect.

The effect of hyperglycemia on glucose kinetics was investigated in normal and T4-treated miniature pigs. 1. T4-treatment increased basal plasma glucose (G) (+ 20%) and glucose turnover (+36%). 2. Glucose infusion (2 mg/kg x min) in controls increased insulin and glucose utilization (Rd), but decreased glucagon and hepatic glucose production (Ra). After T4-treatment glucose increased insulin, decreased glucagon and Ra but only a slight effect on G and Rd were observed. 3. Infusing glucose + somatostatin resulted in hyperglycemia in both groups due to an initial fall in Ra and Rd followed by an increase in Rd, where total Ra (endogenous + exogenous exceeded Rd. Glucose intolerance was more pronounced in controls, due to a T4-induced increase in Rd. During this non-steady state the increment in Rd per increment in G was calculated and showed 1.5 in controls and 2.5 after T4-treatment. These data give evidence that thyroid hormones increase glucose utilization during hypoinsulinemia.

Glucoregulatory function of glucagon in hypo-, eu- and hyperthyroid miniature pigs.

The glucoregulatory function of glucagon was investigated in hypo-, eu- and hyperthyroid miniature pigs. Infusion glucagon, (3 ng x kg body weight-1.min-1) transiently increased blood glucose (p less than 0.01) and hepatic glucose production (p less than 0.01) in euthyroidism, but was without effect in hyperthyroidism. Infusing glucagon plus somatostatin (2 ng x kg body weight-1.min-1 and 0.2 microgram x kg body weight-1.min-1) transiently increased blood glucose (delta 3.0 to 4.3 mmol/l) and hepatic glucose production (delta 3.3 to 7.7 mumol x kg body weight-1.min-1) in all thyroid states, the effect was less pronounced in hyperthyroid pigs. By contrast, hypoglucagonaemia (74 to 107 pg/ml) at basal insulin (28 to 35 microU/ml) provoked hypoglycaemia (1.4 to 2.2 mmol/l) and a fall in glucose production (delta 4.7 to 8.3 mumol x kg body weight-1.min-1), which was independent of the thyroid state; the effect was most pronounced in hyperthyroidism (p less than 0.01). Hepatic glycogen content, arterial gluconeogenic precursor concentrations as well as the glycaemic response (delta 0.60 mmol/l) to alanine infusion (23 mumol x kg body weight-1.min-1) were all unaffected by hyperthyroidism. We conclude that moderate experimental hyperthyroidism reduces glucagon action due to reduced glycogen mobilisation. This may in part result from increased insulin sensitivity.

Liver blood flow measured by indocyanine green in conscious unrestrained miniature pigs.

For studies in physiology and biochemistry of the liver the measurement of hepatic blood flow is a fundamental precondition. Therefore, the least invasive method, the measurement of liver blood flow by indocyanine green (ICG) dye elimination, was re-evaluated for the miniature pig, an animal model of increasing interest. The accuracy of spectrophotometric determination of ICG was enhanced by addition of 5% of desoxycholic acid. It was shown that ICG was eliminated exclusively by the liver. An extraction rate of 30%-50% was found in mini-pigs, but an insufficient rate of 5%-10% in pigs of German landrace. A liver blood flow ranging from 70 to 160 ml/100 g X min-1 was measured. These values are in good accordance with datas from simultaneous estimation of blood flow by 133Xenon washout. As shown for a starvation/refeeding cycle, liver blood flow measurement by ICG combined with permanently implanted catheters is a practicable tool for studies of the metabolic and pharmacologic fate of substances resorbed from the gut.

Serial blood sampling from the portal and hepatic vein in conscious unrestrained miniature pigs.

A technique of implantation of portal and hepatic venous catheters in miniature pigs is described in detail. To overcome early patency loss, Swan-Ganz balloon catheters were used. Portal as well as hepatic venous catheters could be held open to withdraw blood and to apply fluids over a period of at least 50 days. The collected hepatic venous blood represents mixed hepatic outflow. The method is recommended to study absorption of drugs and substrates from the gut and their metabolism in the liver of conscious unrestrained experimental animals.

Effect of ketone bodies on glucose production and utilization in the miniature pig.

The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-beta-OH-butyrate (Na-DL-beta-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, alpha-amino-N, and free fatty acids (FFA) were all reduced. Infusion of Na-bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and alpha-amino-N increased. Infusing different amounts of Na-DL-beta-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed. Prevention of the Na-DL-beta-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 mumol/kg X min) did not prevent hypoglycemia. Infusion of Na-DL-beta-OHB plus insulin (0.4 mU/kg X min) showed no additive effect on the inhibition of Ra. Ketones did not inhibit the insulin-stimulated metabolic clearance rate (MCR) for glucose. Infusion of somatostatin (0.2 micrograms/kg X min) initially decreased plasma glucose, Ra, and Rd, which was followed by an increase in plasma glucose and Ra; however, on infusion of somatostatin plus Na-DL-beta-OHB, hypoglycemia and the reduced Ra were maintained. In the anaesthetized 24-h starved miniature pig, Na-DL-beta-OHB infusion decreased the hepatic exchange for glucose, lactate, and FFA, whereas the exchange for glycerol, alanine, and alpha-amino-N as well as liver perfusion rate were unaffected. Simultaneously, portal glucagon and insulin as well as hepatic insulin extraction rate were elevated. Leg exchange for glucose, lactate, glycerol, alanine, alpha-amino-N, and FFA were decreased, while ketone body utilization increased. Repeated infusion of Na-DL-beta-OHB at the fourth, fifth, and sixth day of starvation in the conscious, unrestrained mini-pig resulted in a significant drop in urinary nitrogen (N)-excretion. However, this effect was mimicked by infusing equimolar amounts of Na-bicarbonate. In contrast, when only the ketoacid was given, urinary N-excretion accelerated. To summarize: (a) Ketone bodies decrease endogenous glucose production via an insulin-dependent mechanism; in addition, ketones probably exert a direct inhibitory action on gluconeogenesis. The ketone body-induced hypoalaninemia does not contribute to this effect. (b) The counterregulatory response to hypoglycemia is reduced by ketones. (c) As a consequence of the decrease in R(a), glucose utilization declines during ketone infusion. (d)The insulin-stimulated MCR for glucose is not affected by ketones. (e) Ketones in their physiological moiety do not show a protein-sparing effect.

Thyroid hormone regulation of glucose homeostasis in the miniature pig.

The effect of different thyroid states on glucose homeostasis was investigated during metabolic adaptation to starvation in the conscious unrestrained miniature pig. Moderate hyperthyroidism increased the rate of glucose turnover, whereas hypothyroidism was without effect. Glucose recycling was elevated in hyperthyroid pigs, and reduced after thyroidectomy. Supplementary doses of T4 normalized total glucose recycling. Glucose metabolic clearance rate and pool size were unaffected by thyroid hormones. During starvation serum insulin showed a similar decrease in all thyroid states; glucagon increased in euthyroid and hypothyroid pigs, although it was already elevated in the hyperthyroid fed state. Serum cortisol levels although varying were enhanced in hyperthyroid and hypothyroid-T4-treated pigs. Glucogenic precursor concentration and cumulative urinary N-excretion were increased in hyperthyroid pigs. It is concluded that 1) even a moderate hyperthyroidism produces an increase in glucose turnover and a concomitant acceleration in protein breakdown, and 2) thyroid hormone is essential for the starvation-induced total glucose recycling.

Glucose production measured by tracer and balance data in conscious miniature pig.

The rate of glucose production was estimated in the conscious, unrestrained miniature pig during metabolic adaptation to starvation (up to 120 h) by the simultaneous use of three different techniques: 1) the isotopedilution technique, 2) the arteriohepatovenous catheter technique, and 3) the urinary nitrogen balance. During the experimental period 1) whole-body glucose turnover decreased, whereas the amount of glucose recycling increased; 2) splanchnic glucose output decreased, whereas the rate of splanchnic precursor extraction increased up to 48 h, followed by a decrease; 3) gut glucose consumption amounted to about 30% of splanchnic glucose output; and 4) urinary nitrogen excretion declined continuously. The comparison of the different methods revealed that during starvation 1) tracer-determined glucose production rate was within the range (+/- 10%) of the splanchnic glucose output; 2) mean hepatic glucose output overestimated the tracer data by about 30-40%; 3) splanchnic glucose output underestimated hepatic glucose production by the amount of gut glucose consumption; 4) tracer-determined glucose recycling corrected for isotope dilution and amino acid contribution was within the range of splanchnic gluconeogenic precursor extractions. Considering the limitations (e.g., gut glucose consumption, gut lactate and alanine release, blood flow measurement) and methodological problems of the different approaches applied, it is evident that each method reflects different events. It is suggested that the versatile tracer technique combined with nitrogen balance should be preferred for measurement of endogenous glucose production.

Alteration in thyroid hormone concentration during and after coronary bypass operation.

The effect of a surgical stress on serum TSH, T4, free T4, T3, rT3 and TBG was measured before, during and after a coronary bypass operation. Precautions were taken to age, sex, pre-operative nutritional state, anamnestic illness, pre- and post-operative medication. Compared to the pre-operative period TSH increased during operation and normalized at the first post-operative day, while only minor alterations for total and free serum T4 were observed. T3 and rT3 declined at the start of extracorporal circulation, T3 remained reduced during the post-operative period, while rT3 reached its pre-operative value at the first post-operative day. It is concluded that the coronary bypass operation evokes a rapid decline in T3, which is not normalized by the TSH induced response of the thyroid gland, while the post-operative period is characterized by a "low T3 state". The clinical relevance of this finding is discussed with respect to the cardiovascular and the nutritional state of the patients in the post-operative period.

Starvation-induced ketone body production in the conscious unrestrained miniature pig.

The effects of short-term starvation (up to 5 days) on hepatic ketone body production was investigated in the conscious unrestrained miniature pig in vivo. Starvation induced an increase in arterial free fatty acid concentration (0.2-0.7 mM) with a concomitant elevation in hepatic free fatty acid extraction [-1.4-5.7 mumol/kg. minute),r = 0.53, P less than 0.005]. Ketone body production (sum of acetoacetate + beta-hydroxybutyrate) increased from 1.5 to 5.8 mumol/(kg . minute) in parallel (r = 0.71, P less than 0.0005). During starvation arterial insulin levels decreased, glucagon increased, cortisol remained unchanged and a "low T3 state' was observed. These data differ in some aspects from those reported for humans and dogs. Thus a species-specific variation in the fuel economy of the pig's body is proposed.

[Effect of afferent abdominal vagus nerve stimulation on the blood circulation and respiration in the guinea pig]. / Uber die Wirkung von afferenter, abdominaler Vagusreizung auf Kreislauf und Atmung des Meerschweinchens

In 38 urethan anesthetized guinea-pigs low frequency (1--30 Hz) electrical afferent stimulation of the abdominal vagus elicited cardiovascular and respiratory reflexes, which were eliminated by bilateral cervical vagotomy: 1. 2/3 of the animals showed a bradycardia with arrhythmia. 1/3 had no heart rate alteration. 2. Biphasic blood pressure alteration with an initial decrease and a following increase was the most common blood pressure response. Longlasting (10 sec) stimulation resulted in a blood pressure increase of 25 to 30 mmHg in 75% of the animals. 3. Acceleration of respiratory rate. A vago-vagal and/or vagosympathetic reflex is considered. It is assumed that the blood pressure curve is composed of adding both the depressor and pressor component. Two functional fibre groups in the afferent abdominal vagus are considered to be the anatomic substratum. Atropine had no effect on the alteration of respiratory rate and blood pressure; only the bradycardia could be eliminated.