Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.     

Kann man balancierte Infusionslösungen verbessern?

Die Anaesthesiologie -     

Erworbene Bauchhöhlenmuskelstörungen

Zusammenfassung Die Bauchhöhle hat ein Faszienskelett, das durch ihren permanenten veränderhchen Ruhetonus verspannt gehalten wird. Zur Bauchhöhle gehören mit der seitlichen Bauchmuskulatur auch das Zwerchfell und der Beckenboden. Willkürliche und reflektorische Tonusänderungen bedingen ihre Verformung und ihren Verschluß oder ihre Eröffnung. Am Versuchstier haben wir diesen Ruhetonus schon in der Schwanzmuskulatur nachgewiesen, von der der Beckenboden des Menschen stammesgeschichtlich abstammt. Der Beckenboden bildet mit den Sphinkteren das anorektale Kontinenzorgan. Es ist, phylogenetisch erklärbar, bei der Frau viel schwächer entwickelt als beim Mann. Diese unterschiedliche Mächtigkeit ist his zu den Kernen des Rückenmarks, die diese Muskulatur steuern, zu verfolgen. Diese Asthenie des weiblichen Kontinenzorgans wird durch das Gebären und die Obstipation noch zusätzlich belastet. Das gleiche gilt für die Bauchdecke der Frau, die, wie hier nachgewiesen wird, nach einer Gravidität die gleichen, bleibenden Denervationserscheinungen ihrer Muskulatur erkennen läß t. Es sind die gleichen Schäden, die der Beckenboden mit den Sphinkteren erleidet. In schwereren Fällen ist neben der Inkontinenz also auch ein Schlotterbauch die Folge dieser Belastungen. Der ruhetonisierte Beckenboden kann das spastische Beckenbodensyndrom, die kontinente Obstipation, zur Folge haben. Sic kann psychotherapeutisch geheilt werden. Davon muß die inkontinente Obstipation unterschieden werden, die manchmal mit einem Mastdarmvorfall einhergeht. Bei ihr liegt das Hindernis im Darm. Sic kann in schweren Fällen durch eine Sigmaresektion gebessert werden. Die Denervationsinkontinenz ist am besten durch das operative Engerstellen des ganzen Levatortrichters zu bessern. Voraussetzung ist: Der gelähmte Beckenboden muß noch eine Restruheaktivität aufweisen.

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Acquired disturbances of muscles of the peritoneal cavity

The peritoneal cavity has a fascial skeleton that is kept under tension by permanent variable resting tone maintained by the abdominal muscles. The lateral abdominal muscles, the diaphragm and the pelvic floor are all components of this fasciomuscular support system. Voluntary and reflective changes in muscle tension allow the entry and exit of matter into and out of the spherical abdominal cavity by opening and closing of specialized wall segments called sphincters. We have previously demonstrated the existence of a resting tone in the tail muscles of mammals from which the human pelvic floor muscles are derived. The pelvic floor and its integrated sphincters form the anorectal organ of continence. This organ is much weaker in females than in males. The spinal centers that govern continence, contain in the female significantly fewer ganglion cells than the corresponding centers in the male. Childbirth and a commonly found tendency to develop constipation are additional stressors for the congenitally weaker female organ of continence. We explain in this paper why the abdominal wall and the pelvic floor may suffer stretch-induced denervation injuries during pregnancy and delivery. Such damage may persist in later life and can give rise to incontinence and flabby abdomen. Based on our work in this field, we found a new differentiation between continent and incontinent constipation. Continent constipation is caused by spasticity of the pelvic floor characterized by abnormally high sphincter activity. This spastic pelvic floor syndrome can be treated successfully by psychotherapeutic techniques. Incontinent constipation, in contrast, is always associated with subnormal activity of the sphincters and may be a cause of rectal prolapse. It can be treated successfully by anterior rectosigmoid resection. Incontinent constipation will also require operative approximation of the levators in many cases. Improvement cannot be expected to result from this procedure, however, unless the pelvic floor shows some residual resting activity.

Korrespondenz an: em. Prof. Dr. Dr. h. c. mult. F. Stelzner     

Parameters influencing piezoelectric shock wave lithotripsy of biliary calculi

A total of 225 human gallbladder stones were divided into sets of two, three, or four identical calculi (with maximum diameters of 6-26 mm) and submitted to piezoelectric shock wave lithotripsy in vitro in order to investigate the influence of the following parameters on stone disintegration: shock wave intensity, pulse frequency, and various physicochemical parameters such as the volume and viscosity of the fluid surrounding the stone, the hardness of the calculus, and its chemical composition. The fragmentation efficacy increased with enhanced shock wave energy (P less than 0.01). If the volume of the fluid (30 mL) surrounding the calculus was small, the disintegration end-point (defined by maximum fragment diameters less than or equal to 4 mm) was achieved after a lower number of pulses (median: 250 pulses) than in the case of a large fluid volume (80 mL) (500 pulses; P less than 0.01). On the other hand, however, factors such as the shock wave pulse rate (0.9 Hz vs 1.6 Hz), variations in viscosity of a water-jelly mixture surrounding the stone, the chemical composition of the stones as determined by X-ray diffractometry, and stone hardness were found to have no significant influence on the fragmentation efficacy.     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation

These experiments examined the role of substance P-selective neurokinin 1 receptors in the restraint-induced activation of the rat locus coeruleus. Immunohistochemistry revealed high levels of neurokinin 1 receptor expression in the plasma membrane of tyrosine hydroxylase-positive locus coeruleus neurons. The selective neurokinin 1 receptor antagonists, RP 67580 (5 nmol) and L-760,735 (3.4 nmol), were administered intracerebroventricularly prior to restraint stress, and c-fos protein was measured as an index of locus coeruleus activation. Both antagonists attenuated the restraint-induced increase in locus coeruleus c-fos expression, whereas their inactive enantiomers were ineffective. These results suggest that neurokinin 1 receptors may mediate activation of locus coeruleus neurons during stress. Neurokinin 1 receptor antagonists may prove to be novel therapeutic compounds in the treatment of anxiety and depression.     

Internal derangements of the shoulder: decision tree and cost-effectiveness analysis of conventional arthrography, conventional MRI, and MR arthrography

Purpose. In a patient with internal derangement of the shoulder, the diagnostic method of choice is controversial. Conventional arthrography can diagnose most rotator cuff tears accurately; however, in many institutions MR arthrography is usually necessary to diagnose labral tears. We utilized decision tree methodology to compare the cost- effectiveness of conventional arthrography and conventional MRI with a hypothetical algorithm in which a patient underwent arthrography, performed with admixed gadolinium, which if negative, was followed by MRI. Design. The use of double-contrast arthrography alone, conventional MRI alone, and gadolinium-enhanced MRI used as an adjunct to conventional arthrography were modeled for the diagnosis of full-thickness rotator cuff tears (RCT), partial RCTs, labral tears, and the absence of cuff/labral tears using decision analysis methodology. English language medical publications were searched to determine the base probabilities for the accuracy of the diagnostic tests. The outcome utilities ranged from –1 to +1 to reflect the value of correct diagnostic evaluation. Charges for diagnostic tests and appropriate surgical treatments were based on 1997 Medicare reimbursement rates for professional fees and hospital charges in an outpatient setting. Sensitivity analyses were performed to evaluate the effects of uncertainty regarding the prevalence of each disease state and the accuracy of several diagnostic tests. Results. In the base-case analysis, the average effectiveness of double-contrast arthrography alone, MRI alone and arthrography selectively followed by MRI were 0.6610, 0.6715, and 0.7204, respectively. The average costs for each of these strategies were $1090, $2033, and $2339, respectively. Conclusion. Arthrography performed with admixed diluted gadolinium, which if negative is immediately followed by MRI, was somewhat more expensive than conventional MRI. However, because of much greater effectiveness, cost-effectiveness was significantly higher for our proposed algorithm. Conventional arthrography without gadolinium, although less expensive, had severely limited effectiveness. Received: 4 June 1999 Revision requested: 6 August 1999 Revision received: 30 August 1999 Accepted: 1 September 1999     

A novel sodium channel mutation in a family with hypokalemic periodic paralysis

OBJECTIVE: To identify the cause of hypokalemic periodic paralysis (HOKPP) in a family whose disease is not caused by a mutation in the dihydropyridine-sensitive (DHP) receptor alpha1-subunit gene (CACNA1S). BACKGROUND: Hypokalemic periodic paralysis is primarily caused by mutations within CACNA1S. Genetic heterogeneity for HOKPP has been reported, but no other locus has been identified. METHODS: Single-stranded conformational polymorphism (SSCP) analysis and PCR direct sequencing were used to screen the skeletal muscle alpha1-sodium channel gene (SCN4A) for a mutation in our family. RESULTS: SSCP analysis showed an abnormally migrating conformer in exon 12. Direct sequencing of the conformer showed a guanine to adenine transition at position 2006 in the cDNA sequence; this results in an amino acid substitution of a highly conserved arginine (Arg) to histidine (His) at position 669. This sequence alteration segregated only with the affected members of the kindred and was not found in a panel of 100 DNA samples from healthy controls. The amino acid substitution alters the outermost positive charge in the membrane spanning segment DII/S4, which is involved in voltage sensing. CONCLUSIONS: The first arginine in DII/S4 and in DIV/S4 within the skeletal muscle sodium channel and the L-type calcium channel genie CACNA1S appear to be critical for normal function. In all four cases, Arg to His mutations result in a disease phenotype. The identification of a mutation within the skeletal muscle sodium channel resulting in hypokalemic periodic paralysis represents a novel finding.     

The transurethral resection syndrome

The transurethral resection syndrome ("TUR syndrome") is caused by absorption of electrolyte-free irrigating fluid, and consists of symptoms from the circulatory and nervous systems. The clinical picture is inconsistent and the syndrome is easily confused with other acute disorders. Mild forms are common and often go undiagnosed, while severe forms of the TUR syndrome are rare and potentially life-threatening. The pathophysiology is complex but includes four mechanisms: circulatory distress from the rapid absorption of electrolyte-free irrigating fluid, adverse effects of glycine, dilution of the protein and electrolyte concentrations of the body fluids, and disturbance of renal function. The treatment of the TUR syndrome consists of general life support and in specific treatment directed towards hypotension, hyponatraemia and anuria. Methods to lower the uptake of irrigating fluid are widely used and probably reduce the incidence of the TUR syndrome. However, patient safety can be guaranteed only if the absorption is monitored. An irrigating fluid containing tracer amounts of ethanol can be used for this purpose. This permits the uptake of fluid to be indicated by measuring the concentration of ethanol in the patient's exhaled breath.