Peter Kühl

Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome.

A congenital hypokalemic tubular disorder is described with many features resembling Bartter syndrome. Additional features include prenatal onset with polyhydramnios and premature labor; failure to thrive; episodes of fever, vomiting, diarrhea, and renal electrolyte and water wastage; hypercalciuria; nephrocalcinosis; and osteopenia. Unlike Bartter syndrome, there is no defect in tubular reabsorption of chloride. Urinary levels of prostaglandin E2 and 7 alpha-hydroxy-5,11-diketotetranorprosta-1,16-dioic acid are selectively elevated, indicating marked stimulation of renal and systemic PGE2 production. Chronic suppression of PGE2 activity by indomethacin corrects most of the abnormalities, and there is an immediate decompensation of the disease on indomethacin withdrawal. We conclude that these preterm infants have a distinct variety of hypokalemic tubular disorders rather than a variant of Bartter syndrome, because renal and systemic hyperprostaglandinism ranks high in the pathogenic chain of events, and the suppression of PGE2 hyperactivity is associated with significant improvement in the development (and probably in the prognosis) of the affected children.

A real-time algorithm for moving horizon state and parameter estimation

Abstract A moving horizon estimation (MHE) approach to simultaneously estimate states and parameters is revisited. Two different noise models are considered, one with measurement noise and one with additional state noise. The contribution of this article is twofold. First, we transfer the real-time iteration approach, developed in Diehl et al. (2002) for nonlinear model predictive control, to the MHE approach to render it real-time feasible. The scheme reduces the computational burden to one iteration per measurement sample and separates each iteration into a preparation and an estimation phase. This drastically reduces the time between measurements and computed estimates. Secondly, we derive a numerically efficient arrival cost update scheme based on one single QR-factorization. The MHE algorithm is demonstrated on two chemical engineering problems, a thermally coupled distillation column and the Tennessee Eastman benchmark problem, and compared against an Extended Kalman Filter. The CPU times demonstrate the real-time applicability of the suggested approach.

Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders

Renal and systemic prostanoid activity was assessed in various renal tubular disorders, using mass spectrometric determination of urinary excretion rates of primary prostaglandins (PGE2, PGF2α, PGI2, and TXA2) and their systemically produced index metabolites. Only PGE2 levels (normal range: 2.0–16.4 ng/h per 1.73 m2) are elevated in Bartter syndrome (median: 43.4, range: 6.7–166.3), nephrogenic diabetes insipidus (46.2, 12.1–1290), Fanconi syndrome (96.6, 19.3–135.5), and in a complex tubular disorder in premature infants (40.7, 22.3–132.1), for which the term hyperprostaglandin E syndrome has been introduced. In this disorder with a Bartter-syndrome-like tubulopathy, the systemic features of the disease such as fever, diarrhoea and osteopenia with hypercalciuria were associated with increased systemic PGE2 activity. In most patients the urinary excretion rate of the systemic index metabolite of PGE2 (PGE-M) was markedly elevated (1028, 285–4709; normal range: 104–664 ng/h per 1.73 m2). Hypercalciuria per se was associated neither with increased renal nor with systemic PGE2 hyperactivity. Most problems in infants with hyperprostaglandin E syndrome could be controlled by long-term indomethacin treatment in contrast to the moderate and partial effect of this treatment in patients with Fanconi syndrome. Thus increased PGE2 synthesis plays a major role in the pathogenesis of hyperprostaglandin E syndrome, while in Fanconi syndrome PGE2 hyperactivity in the kidney is a secondary event and only aggravates the water and electrolyte wastage.

A Moving Horizon State Estimation algorithm applied to the Tennessee Eastman Benchmark Process

A moving horizon state estimation algorithm (MHE) is applied to the nonlinear and unstable Tennessee Eastman process, a well-known benchmark problem in the chemical process engineering community. The estimator fuses past measurements within a given time horizon and calculates the actual states in a maximum-likelihood fashion. The calculations are based on a first-principles process model. The arising least-squares optimization problem is solved numerically by the direct multiple shooting technique. Due to an intelligent real-time iteration approach, estimation CPU times lie between 0.5 and 4.5 seconds on a standard PC. Furthermore, an upper bound of the CPU time needed for one estimation task can be determined a priori. This makes the proposed MHE a true real-time algorithm for state estimation

Extracorporeal circulation increases nitric oxide-induced methemoglobinemia in vivo and in vitro.

OBJECTIVES Methemoglobinemia is a well-known side effect of nitric oxide inhalation. We tested the hypothesis whether cardiopulmonary bypass increases methemoglobin formation by nitric oxide. DESIGN A two-phase study: a) a controlled, prospective in vivo study of inhaled nitric oxide treatment followed by b) a second, prospective and controlled in vitro study. SETTING Pediatric intensive care unit and research laboratory in a university hospital. PATIENTS The in vivo study consisted of 25 patients following open-heart surgery and 19 children with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn. The in vitro study consisted of 20 patients with and 20 patients without cardiopulmonary bypass. INTERVENTIONS For the in vivo study, methemoglobin measurements were taken before and after application of 20 parts per million (ppm) of nitric oxide. For the in vitro study, red blood cells of patients were incubated with 32 ppm nitric oxide before and after surgery. Methemoglobin, glutathione, adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADHP) concentrations were compared. MEASUREMENTS AND MAIN RESULTS For the in vivo study, nitric oxide inhalation increased methemoglobin from 0.2 +/- 0.1% to 1.2 +/- 0.7% in patients receiving nitric oxide after open-heart surgery and from 0.2 +/- 0.1% to 0.5 +/- 0.4% in ARDS/persistent pulmonary hypertension of the newborn patients (p < .01). For the in vitro study, nitric oxide incubation of red blood cells increased methemoglobin concentration from 3.7 +/- 1.9% preoperatively to 7.4 +/- 2.4% after open-heart surgery. This increase was not observed in patients who did not undergo cardiopulmonary bypass (3.6 +/- 1.6% vs. 3.6 +/- 1.9%; p < .001). In erythrocytes of patients undergoing extracorporeal circulation, there was no difference between pre- and postoperative glutathione, ATP, and NADH/NADPH concentrations. CONCLUSIONS Cardiopulmonary bypass is an important risk factor for methemoglobinemia when inhaled nitric oxide is applied. This risk is not secondary to diminished concentrations of energetic substrates.

Increased Renal Biosynthesis of Prostaglandin E2 and Thromboxane B2 in Human Congenital Obstructive Uropathy

ABSTRACT: Animal experiments have shown that after ureter obstruction hydronephrotic kidneys release increased amounts of prostaglandin E2(PGE2) and thromboxane A2 (TxA2), suggesting that these prostanoids modify renal blood flow and excretory function in this model. To test the hypothesis that these mechanisms are also operative in congenital obstructive uropathy, we measured prostanoid excretion rates in 12 neonates and infants with congenital unilateral or bilateral hydronephrosis. Prostanoid determinations were performed by gas chromatography mass spectrometry. PGE2 and thromboxane B2 (TxB2) (non-enzymatic metabolite of TxA2) excretion exceeded the normal range in eight and 11 of 12 patients, respectively. Median PGE2 excretion was 22, range 4-572 ng/h/1.73 m2 (normal 3-16). Median TxB2 excretion was 22, range 3-188 ng/h/1.73 m2 (normal 3-7). No other renal prostanoids (prostaglandin F2α, 6-keto-prostaglandin F1α) or systemic prostanoid metabolites (PGE-M, 2,3-dinorthromboxane B2, 11-dehydro-thromboxane B2, 2,3-dinor- 6-keto-prostaglandin F1α) were consistently elevated. A second group of 12 neonates with congenital obstructive uropathy was followed sequentially. PGE2 and thromboxane B2 excretion rates increased even further after surgical decompression and gradually normalized during follow-up. There was a significant relationship between elevated FeNa and enhanced PGE2 and TxB2 excretion. These data suggest that endogenous renal formation of PGE2 and TxA2 is selectively stimulated in hydronephrotic kidneys in neonates and infants. PGE2 and TxA2 may be involved in modulating renal function in these infants.

An Adjoint-Based Numerical Method for Fast Nonlinear Model Predictive Control

Abstract The application of optimization-based control methods such as nonlinear model predictive control (NMPC) to real-world process models is still a major computational challenge. In this paper, we present a new numerical optimization scheme suited for NMPC. The SQP-type approach uses an inexact constraint Jacobian in its iterations and is based on adjoint derivatives, that can be computed very efficiently. In comparison to a similar real-time algorithm based on directional sensitivities and an exact constraint Jacobian, the computational complexity is significantly reduced. Both algorithms are applied to the model of a thermally coupled distillation column for disturbance rejection. The results provide a proof-of-principle for the proposed adjoint-based optimization approach.

Numerical Methods for Efficient and Fast Nonlinear Model Predictive Control

The paper reports on recent progress in the real-time computation of constrained closed-loop optimal control, in particular the special case of nonlinear model predictive control, of large di.erential algebraic equations (DAE) systems arising e.g. from a MoL discretization of instationary PDE. Through a combination of a direct multiple shooting approach and an initial value embedding, a so-called “real-time iteration” approach has been developed in the last few years. One of the basic features is that in each iteration of the optimization process, new process data are being used. Through precomputation – as far as possible – of Hessian, gradients and QP factorizations the response time to perturbations of states and system parameters is minimized. We present and discuss new real-time algorithms for fast feasibility and optimality improvement that do not need to evaluate Jacobians online.

Schnelle Algorithmen für die Zustands- und Parameterschätzung auf bewegten Horizonten (Fast Algorithms for State and Parameter Estimation on Moving Horizons)

Wir behandeln das Problem einer gleichzeitigen Zustands- und Parameterschätzung auf bewegtem Horizont (Moving Horizon Estimation, MHE). Wir schlagen eine MHE Formulierung für differential-algebraische Systemmodelle vor, die deterministisches Systemverhalten auf dem Schätzhorizont annimmt und eine Regularisierung des Anfangswertes verwendet. Zu ihrer numerischen Lösung stellen wir effiziente Methoden zur schnellen On-line-Lösung der MHE Probleme vor, die auf dem Mehrzielverfahren für die Parameterschätzung beruhen. In der vorgeschlagenen MHE Echtzeititeration wird zu jedem MHE Optimierungsproblem nur eine einzige Optimierungsiteration durchgeführt, und die aufeinander folgenden Probleme werden durch ein Verschieben der bereits geschätzten Trajektorie effizient initialisiert. Die Methode wird auf das Problem zweier thermisch gekoppelter Destillationskolonnen angewandt und mit einem erweiterten Kalman-Filter verglichen. Neben dem Systemzustand aus über 400 Variablen werden drei veränderliche Betriebsparameter mitgeschätzt. Die Rechenzeiten für dieses schwierige Problem liegen bei rund 5 Sekunden pro MHE Optimierung. We treat the problem of moving horizon state and parameter estimation (MHE) and propose a formulation for differential-algebraic systems that assumes a deterministic system behaviour on the estimation horizon, and which uses a regularization of the initial value. We present an efficient method for fast online solution of the subsequent MHE problems. The method is based the multiple shooting method for parameter estimation. The proposed MHE real-time iteration scheme performs only a single optimization iteration for each new MHE optimization problem. Subsequent problems are initialized via a shift of the best available trajectory estimate. The method is applied to the problem of two thermally coupled distillation columns and compared to an extended Kalman Filter. In addition to the system state of over 400 variables we also estimate three varying feedflow parameters. The algorithm uses a CPU time of around 5 seconds per MHE optimization for this challenging application.

Accuracy of methemoglobin measurements: comparison of six different commercial devices and one manual method.

OBJECTIVE During nitric oxide inhalation, methemoglobinemia needs to be monitored. We compared six commercially available instruments and one manual method for methemoglobin measurements. In addition, we studied whether and to what degree methylene blue interferes with methemoglobin measurements. DESIGN In vitro methodologic study. SETTING Research laboratory in a university hospital. PATIENTS Five healthy volunteers from whom red blood cells were obtained. INTERVENTIONS Methemoglobinemia was generated in a red blood cell suspension by nitric oxide; methemoglobin was measured with six commercial instruments and one manual photometric method to calculate variation coefficients and to determine the differences between the devices. Methemoglobin was measured with and without the addition of methylene blue with two instruments. Measurements were performed immediately after the addition of methylene blue. MEASUREMENTS AND MAIN RESULTS All six commercially available instruments had variation coefficients of <0.1 at methemoglobin concentrations of 5%, whereas the manual photometric method did not reach a variation coefficient of <0.1 at 8% of methemoglobin. Apart from two devices that measured slightly but significantly higher methemoglobin levels, all instruments measured similar values of methemoglobin when the same samples were determined simultaneously. Higher concentrations of methylene blue (10, 40, 100 microM) reduced substantially the apparent concentrations of methemoglobin. Interference by methylene blue was most pronounced at low methemoglobin levels. CONCLUSIONS With some limitations, all commercial instruments that were tested performed adequately for the monitoring of methemoglobinemia. Methylene blue interferes with the methemoglobin measurements in a dose-dependent manner.