[Morning hyperglycemia in children and adolescents with type 1 diabetes and different modes of therapy: an evaluation of the DPV data pool]. / Morgenhyperglykämie bei Kindern und Jugendlichen mit Typ-1-Diabetes bei unterschiedlichen Therapieformen: Eine Auswertung des DPV-Datenpools.

Early morning hyperglycemia is frequent among children and adolescents with type 1 diabetes. Reasons are a dawn phenomenon, a Somogyi phenomenon or a lack of insulin in the morning hours. Only few studies are published regarding incidence and relation to different modes of basal insulin treatment in this population.We analyzed all cases recorded in the DPV register from 1995 to 2010. 5 839 patients from 128 centers with at least 3 blood glucose measurements during the last night of a hospital stay were included.24.2% of patients showed a morning hyperglycemia above 200 mg/dl. 8.6% showed a dawn phenomenon, 7.0 % a lack of insulin and 2.0% a Somogyi phenomenon. A dawn phenomenon was significantly less frequent in patients treated with an insulin pump (1.1%) compared to long acting insulin analogs Glargin and Levemir (5.4%) or NPH insulin (8.2%). Lack of insulin was again less frequent during insulin pump treatment compared to other treatments (1.9% vs. 4.9% vs. 5.3%). Median rise of blood glucose levels was 33.4 mg/dl between midnight and 6 a.m. Mode of basal insulin treatment is an important factor: while treatment with an insulin pump led to a blood glucose fall of 28.5 mg/dl between 3 and 6 a.m., treatment with insulin analog or NPH insulin resulted in a rise of 28.5 or 35.9 mg/dl, respectively.This study shows that insulin pump treatment reduces the frequency of morning hyperglycemia caused by the dawn phenomenon or a lack of insulin.

[Clinical parameters for molecular testing of Maturity Onset Diabetes of the Young (MODY)]. / Molekulargenetische Diagnostik bei Verdacht auf Maturity Onset Diabetes of the Young (MODY): Klinische Parameter zur Entscheidungshilfe.

BACKGROUND: Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening. METHODS: Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria. RESULTS: Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment. CONCLUSION: In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment.

Synaptonemal complex protein SYCP3 exists in two isoforms showing different conservation in mammalian evolution.

Meiosis-specific protein SYCP3 is a major structural component of synaptonemal complex (SC) lateral elements. SYCP3 is rather well conserved in vertebrates. However, some differences in SYCP3 expression have been shown among mammals. To clarifiy these differences, we have investigated SYCP3 expression with the aid of bioinformatic, biochemical and cell biological methods. Here we show that, in contrast to other vertebrates, rat and mouse SYCP3 exist in 2 isoforms. The short isoform is conserved among vertebrates. However, the longer isoform, which represents an N-terminal extension of the shorter one, most likely appeared about 15 million years ago in a common ancestor of rat and mouse and after separation from the hamster branch.

[Left ventricular diastolic dysfunction. Implications for anesthesia and critical care]. / Linksventrikuläre diastolische Dysfunktion. Bedeutung in Anästhesie und Intensivmedizin.

Over the last two decades there has been a growing recognition that cardiac function is not solely determined by systolic but also essentially by diastolic function. Left ventricular diastolic dysfunction is characterized by an impairment of ventricular filling caused either by abnormal relaxation, an active energy consuming process or decreased compliance, which is determined by passive tissue properties of the ventricle. Doppler echocardiography, including tissue Doppler imaging, has emerged as the preferred clinical tool for the assessment of left ventricular diastolic function. Recently the importance of left ventricular diastolic function is increasingly being recognized also during the perioperative period. Newer studies have shown that after cardiopulmonary bypass there is a significant decrease in left ventricular compliance. Experimental studies have demonstrated that sepsis is associated with a decrease in both active relaxation and ventricular compliance. Initial studies are also focusing on therapeutic options for patients with isolated diastolic dysfunction.

Seed dormancy, after-ripening and light requirements of four annual Asteraceae in south-western Australia.

The role of dormancy, temperature and light in the regulation of seed germination of four annual Asteraceae from south-western Australia was investigated. The experiments aimed to identify after-ripening patterns, and to relate these to climatic conditions of the habitat in which the species occur. Seeds of all species were strongly dormant at maturity and maintained high levels of dormancy for time periods corresponding to the duration of summer in south-western Australia. Dry after-ripening was promoted best by temperatures lower than those prevailing in the dry season, although differences among storage temperatures were mostly insignificant. Germination percentages were highest at average winter temperatures (15 degrees C). A logistic model revealed significant differences in germinability among species, but not between incubation temperatures or light and dark treatments across species. Three species with seeds >0.5 mg germinated better in darkness than in light, whereas germination in darkness was almost inhibited in the species with the smallest seeds (0.14 mg). The course of dormancy loss, tested over a range of fluctuating incubation temperatures (7-30 degrees C), showed that seeds of three species came out of dormancy first at temperatures that prevail in south-western Australia during the winter (10-15 degrees C). Seeds from one species, introduced from South Africa, first lost dormancy at the lowest temperature (7 degrees C). All species showed after-ripening patterns of Type 1, typical of species growing in Mediterranean climates. The germination characteristics of the investigated species can be interpreted as ensuring that initial growth and establishment occur during the winter growing season, thereby avoiding the hot and dry summer conditions that follow seed dispersal.

Noninvasive diagnosis of coronary artery disease: a comparison between cardiokymographic and electrocardiographic stress testing.

Noninvasive cardiokymography has been further developed to be able to record wall motion abnormalities during exercise. The study was designed to evaluate the diagnostic accuracy of stress cardiokymography and electrocardiography in the diagnosis of coronary artery disease. 223 patients were included in a prospective investigation using a newly developed computerized cardiokymography device. Sensitivity, specificity, and positive predictive value were 61, 69 and 90% for exercise cardiokymography, and 57, 74 and 91% for exercise electrocardiography, respectively. There was no statistically significant difference between cardiokymography and electrocardiography. The combination of electrocardiography and cardiokymography did not produce a significant improvement in diagnostic accuracy in comparison to exercise electrocardiography alone.

Is it feasible to monitor total hepatic blood flow by use of transesophageal echography? An experimental study in pigs.

OBJECTIVES: Total hepatic venous blood flow is determined by the common hepatic arterial blood flow and the venous outflow from stomach, spleen, pancreas, small intestine, and bowel, collected by the portal vein, and thus represents overall splanchnic perfusion. We investigated whether transesophageal echography (TEE) can provide a method for bedside assessment of hepatic venous blood flow useful as a noninvasive method for measuring splanchnic perfusion in clinical practice. DESIGN AND SETTING: Experimental study in 15 anesthetized and ventilated pigs in an animal research laboratory. INTERVENTIONS: TEE-derived calculations of hepatic venous blood flow were compared with liver blood flow measurements using perivascular ultrasound flow probes surgically positioned on portal vein and common hepatic artery. Parameters were determined at baseline and after modulating splanchnic perfusion by either PEEP maneuver (15 cmH2O) or intravenous epinephrine (0.1 microgram kg-1 min-1). MEASUREMENTS AND RESULTS: Diameter (d) and velocity time integral (VTI) of all three hepatic veins were determined by TEE, heart rate (HR) was derived from electrocardiography and flow subsequently calculated as Q = pi.(d/2)(2).0.57.VTI.HR. Regression analysis of matched TEE and flow probe values showed a significant linear relationship (r2 = 0.698). Bias analysis revealed a systematic underestimation of liver blood flow by TEE, possibly due to use of 0.57 as correction factor for mean velocity, while changes in liver blood flow were reliably detected. CONCLUSION: TEE offers a noninvasive approach for monitoring hepatic perfusion and may be used in patients.

Electrocardiographic exercise stress testing for cardiac risk assessment in patients undergoing noncardiac surgery.

BACKGROUND: The value of exercise electrocardiography in the prediction of perioperative cardiac risk has yet to be defined. This study was performed to determine the predictive value of exercise electrocardiography as compared with clinical parameters and resting electrocardiography. METHODS: A total of 204 patients at intermediate risk for cardiac complications prospectively underwent exercise electrocardiography before noncardiac surgery. Of these, 185 were included in the final evaluation. All patients underwent follow-up evaluation postoperatively by Holter monitoring for 2 days, daily 12-lead electrocardiogram, and creatine kinase, creatine kinase MB, and troponin-T measurements for 5 days. Cardiac events were defined as cardiac death, myocardial infarction, minor myocardial cell injury, unstable angina pectoris, congestive heart failure, and ventricular tachyarrhythmia. Potential risk factors for an adverse event were identified by univariate and multivariate logistic regression analysis. RESULTS: Perioperative cardiac events were observed in 16 patients. There were 6 cases of myocardial infarction and 10 cases of myocardial cell injury. The multivariate correlates of adverse cardiac events were definite coronary artery disease (odds ratio, 8.8; 95% confidence interval [CI], 1.1--73.1; P = 0.04), major surgery (odds ratio, 4.7; 95% CI, 1.3--16.3; P = 0.02), reduced left ventricular performance (odds ratio, 2.0; 95% CI, 1.1--3.8; P = 0.03), and ST-segment depression of 0.1 mV or more in the exercise electrocardiogram (odds ratio, 5.2; 95% CI, 1.5--18.5; P = 0.01). A combination of clinical variables and exercise electrocardiography improved preoperative risk stratification. CONCLUSIONS: This prospective study shows that a ST-segment depression of 0.1 mV or more in the exercise electrocardiogram is an independent predictor of perioperative cardiac complications.

Use of multi-plane transoesophageal echocardiography in visualization of the main hepatic veins and acquisition of Doppler sonography curves. Comparison with the transabdominal approach.

The role of multi-plane transoesophageal echocardiography (TOE) in the visualization of the three main hepatic veins and acquisition of Doppler sonography curves has not been established. We have studied this diagnostic option of TOE in 34 patients during general anaesthesia. The findings were compared with the results of conventional transabdominal sonography (TAS). Using TOE, each of the three main hepatic veins could be visualized in all patients. In contrast, TAS allowed adequate two-dimensional visualization of the right, middle, and left hepatic vein in only 97%, 85%, and 61% of the patients, respectively. Adequate Doppler tracings of the right and middle hepatic vein could be obtained in 100% and 97% of the patients by TOE and in 91% and 50% of the patients by TAS. Doppler tracings of the left hepatic vein could only be acquired in 18% of the patients by TOE, but in 47% of the patients by TAS. As blood flow may be calculated from the diameter of the vessel, velocity time integral of the Doppler curve and heart rate, TOE may provide an interesting non-invasive tool to monitor blood flow in the right and middle hepatic vein.

The disability assessment database model.

Collecting disability-related information in order to prevent and treat specific disabilities is important and necessary, but does it meet the major needs of individuals with disabilities? This article presents preliminary research performed to assess those needs as well as a Disability-service Assessment Database (DAD) model. This model provides local disability service data and surveys users so that their input is used to modify existing data. The content of the database and Web site are discussed and diagramed. A major goal of the DAD is to serve as a model to other communities.

[The basics of catecholamine therapy. 2. A guide to clinical use]. / Grundsätze der Katecholamintherapie. Teil 2: Leitfaden der klinischen Anwendung.

Myocardial function is determined by preload, afterload, contractility and heart rate. Pathologic changes of these variables may result in decrease of blood pressure, acute heart failure or cardiogenic shock. Hyperdynamic septic shock is associated with systemic hypotension despite increased cardiac output. Mediators of sepsis induce both myocardial depression and pulmonary arterial hypertension. Moreover, sepsis is characterized by microcirculatory disturbances and dysbalance in regional oxygen delivery and consumption. Severe systemic hypotension is a symptom often requiring catecholamine therapy to restore systemic circulation and to avoid organ damage. As the use of catecholamines is not a causal therapy administration should be limited to an initial measure until correction of the underlying abnormalities can be achieved. Different etiologies of shock as well as diseases requiring specific interventions as pulmonary embolectomy, systemic lysis or coronary angioplasty have to be considered. First line intervention consists of optimizing preload by fluid resuscitation as appropriate and use of dopamine (4-12 micrograms/kg.min) as primary catecholamine to increase contractility and blood pressure. In acute left heart failure inotropic support with dobutamine (4-12 micrograms/kg.min) or epinephrine (0.05-1 microgram/kg.min) may be necessary, frequently combined with a vasodilator (sodium nitroprusside 0.2-5 micrograms/kg.min or nitroglycerine 0.5-2.5 micrograms/kg.min) or phosphodiesterase-III-inhibitor (milrinone 0.3-0.8 microgram/kg.min). In right heart failure norepinephrine is preferred to increase coronary perfusion pressure. Hyperdynamic septic shock with decreased vascular resistance is treated with norepinephrine to restore mean arterial pressure and to improve right ventricular dysfunction induced by pulmonary hypertension.

[Principles of catecholamine therapy. 1. Characterization of clinically relevant sympathomimetics]. / Grundsätze der Katecholamintherapie. Teil 1: Charakterisierung der therapeutisch bedeutsamen Sympathomimetika.

All involuntary innervated structures of the body are controlled by the sympathetic and parasympathetic nervous system. Adrenaline, noradrenaline and dopamine are endogenous catecholamines binding to adrenergic and dopaminergic receptors, respectively, to mediate their clinical effects. Adrenoceptors are classified as alpha 1, alpha 2, beta 1 and beta 2 subtypes which were even further subcharacterized the recent years. Adrenoceptors are membrane proteins interacting with the agonist and, thus, inducing G-protein mediated intracellular effects. Adrenaline induces an extensive increase of heart rate and stroke volume mediated by beta-adrenoceptors and significantly enhances peripheral vascular resistance by alpha-adrenoceptor stimulation, when administered beyond 0.1 microgram/kg.min. In contrast, the clinical effects of noradrenaline are predominantly characterized by alpha-adrenoceptor stimulation resulting in a less pronounced increase of heart rate. Dopamine, less potent on adrenoceptors, shows additional effects on renal as well as on splanchnic circulation mediated by dopaminergic receptors. Dobutamine, primarily acting on beta-adrenoceptors, results in positive inotropic effects without an increase in vascular resistance. Dopexamine, a synthetic catecholamine, induces vasodilation via beta 2-adrenoceptor stimulation and potentially increases splanchnic blood flow by additional effects on dopaminergic receptors. Isoproterenol, the classical beta-adrenoceptor agonist, mediates positive inotropic effects and causes a major increase in heart rate and a significant decrease of systemic vascular resistance. Independent on adrenoceptors, phosphodiesterase-III-inhibitors exert positive inotropic and vasodilating activity by an increase in intracellular cAMP concentration induced by inhibition of cAMP hydrolysis.

Perioperative transcutaneous pacemaker in patients with chronic bifascicular block or left bundle branch block and additional first-degree atrioventricular block.

BACKGROUND: Complete heart block is dreaded perioperatively in patients with chronic bifascicular or left bundle branch block (LBBB) and additional first-degree A-V block. Our aim was to investigate the necessity as well as the efficacy and safety of transcutaneous pacing in the perioperative setting. METHODS: Thirty-nine consecutive patients with asymptomatic chronic bifascicular block or LBBB and prolongation of the P-R interval scheduled to undergo surgery under anesthesia were prospectively enrolled in the study. Preoperatively, a transcutaneous pacemaker (PACE 500 D, Osypka Co.) was applied; its efficacy was checked with intra-arterial blood pressure measurement; the pain level was recorded. Additionally, 24-h Holter monitoring (CM2, CM5) was applied. Occurrences of a block progression or a bradycardia of <40 beats/min with hemodynamic impairment were the defined end points. RESULTS: Thirty-seven of the 39 patients (95%) could be successfully stimulated with a median current strength of 70 mA; whereby 33 of the 39 patients felt moderate to severe pain. There was no perioperative block progression. Three cases of brady-cardia of <40 beats/min with a critical drop in blood pressure occurred; but these patients were successfully treated with drug therapy without pacemaker stimulation. CONCLUSION: The perioperative application and testing of the pacemaker was safe and could be performed in nearly all patients successfully. However, we do not consider a routine prophylactic transcutaneous placement in patients with chronic bifascicular or LBBB and additional first-degree A-V block justified. Nevertheless, appropriate drugs and temporary pacemaker equipment should be easily accessible.

[Development of a new closed-loop system for controlling mivacurium-induced neuromuscular blockade]. / Entwicklung eines neuen Closed-Loop Systems. Regelung einer Mivacurium-induzierten neuromuskulären Blockade.

UNLABELLED: There are many closed-loop control systems for muscle relaxants reported, but only a few could cope with the introduction of the latest shorter acting neuromuscular blocking drugs. These new muscle relaxants such as mivacurium require a fast adapting closed-loop system for controlling an adequate infusion. METHODS: After approval of the local ethics committee and having the patients' informed consent a total number of 75 patients [ASA I and II] were included in the study and assigned either to a training-, prediction-, prediction-/feedback- or a validation phase, as needed. Anaesthesia was induced and maintained with propofol in a TCI-mode with a plasma level of 3 to 5 micrograms/ml and 0.1 mg fentanyl boli as needed in all patients. In the last validation phase, having 20 patients, the prediction error and the error of the whole system was taken and analysed. RESULTS: A closed-loop system using a neural network as a predictor could be established. In the final validation phase consisting of 20 patients the mean square prediction error was found to be 0.1% +/- 0.2% [mean +/- SD]. The mean square error of the whole system was 0.55% +/- 0.59% [mean +/- SD]. CONCLUSIONS: A closed-loop system for control of a mivacurium infusion could be established. The system proofed to be reliable for a closed-loop infusion of mivacurium in order to maintain a predefined degree of neuromuscular blockade of 95% during routine surgery. The performance of the described controller is comparable to all recent attempts and could therefore be useful for scientific studies. It should be further validated and established for other muscle relaxants, as well.

Perioperative risk of bradyarrhythmias in patients with asymptomatic chronic bifascicular block or left bundle branch block: does an additional first-degree atrioventricular block make any difference?

BACKGROUND: The incidence of perioperative bradyarrhythmias in patients with bifascicular or left bundle branch block (LBBB) and the influence of an additional first-degree atrioventricular (A-V) block has not been evaluated with 24-h Holter electrocardiographic monitoring. Therefore the authors assessed the rate of block progression and bradyarrhythmia in these patients. METHODS: Patients (n = 106) with asymptomatic bifascicular block or LBBB with or without an additional first-degree A-V block scheduled for surgery under general or regional anesthesia were enrolled prospectively. Three patients were excluded. Of the 103 remaining, 56 had a normal P-R interval and 47 had a prolonged one. Holter monitoring (CM2, CM5) was applied to each patient just before induction of anesthesia and was performed for 24 h. The primary endpoint of the study was the occurrence of block progression. As secondary endpoints, bradycardias < 40 beats/min with hemodynamic compromise (systolic blood pressure < 90 mmHg) or asystoles > 5 s were defined. RESULTS: Block progression to second-degree A-V block and consecutive cardiac arrest occurred in one case of LBBB without a prolonged P-R interval Severe bradyarrhythmias with hypotension developed in another eight patients: asystoles > 5 s occurred in two cases and six patients had bradycardias < 40/min. Pharmacotherapy was successful in these eight patients. There was no significant difference for severe bradyarrhythmias associated with hemodynamic compromise between patients with and without P-R prolongation (P = 1.00). CONCLUSIONS: In patients with chronic bifascicular block or LBBB, perioperative progression to complete heart block is rare. However, the rate of bradyarrhythmias with hemodynamic compromise proved to be relevant. Because an additional first-degree A-V block did not increase the incidence of severe bradyarrhythmias and pharmacotherapy by itself was successful in nearly all cases, routine prophylactic insertion of a temporary pacemaker in such patients should be questioned.

Usefulness of chromogranin A as a marker for detection of relapses of carcinoid tumours.

It is well known that peptide-producing endocrine tumours cosecrete immunoreactive chromogranin A with their characteristic hormones. Into this study 187 patients with the diagnosis malignant carcinoids or other malignancies were entered. Using chromogranin A at a cut-off level of 30.3 U/ml it was possible to discriminate between patients in remission and patients suffering a relapse with a sensitivity of 91.7% and a specificity of 96.4%, which may be of important diagnostic value. In our study that lasted over one year we could clearly show that the measurement of chromogranin A is impressively superior to 5-hydroxyindoleacetic-acid for detecting a relapse of carcinoids.