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Biomedical subjects

P Ott

Publications and source records attributed to P Ott.

At least 55 records · Page 3Linked to original sources
PubMed1999

The effect of increasing blood pressure with dopamine on systemic, splanchnic, and lower extremity hemodynamics in patients with acute liver failure.

BACKGROUND: Arterial hypotension occurs frequently in patients with acute liver failure (ALF). Treatment with epinephrine and norepinephrine in patients with ALF has been associated with a decrease in whole-body (systemic) oxygen consumption. We aimed to investigate the effect of increasing blood pressure with dopamine on whole-body (systemic), splanchnic, and lower extremity hemodynamics and oxygen consumption in patients with acute liver failure and hepatic encephalopathy grade III or IV. METHODS: In seven patients with ALF cardiac output (CO) was measured with the thermodilution technique, and hepatic blood flow (HBF) was estimated with infusion of sorbitol as test compound, liver vein catheterization, and calculations on the basis of Fick's principle. Lower-extremity blood flow was measured with strain-gauge plethysmography. RESULTS: During infusion of dopamine (5 +/- 2 microg kg(-1) min(-1)) mean arterial pressure (MAP) increased from 68 +/- 5 to 85 +/- 8 mmHg. CO increased from 6.8 +/- 0.8 to 9.0 +/- 2.4 l/min (P < 0.05), systemic oxygen delivery from 45 +/- 7 to 63 +/- 19 mmol/min (P < 0.05), systemic oxygen consumption from 10.2 +/- 2.0 to 11.5 +/- 3.3 mmol/min (NS). HBF increased from 2.2 +/- 0.7 to 2.7 +/- 1.0 l/ min (P < 0.05), splanchnic oxygen delivery from 14.4 +/- 5.3 to 18.5 +/- 7.2 mmol/min (P < 0.01), and splanchnic oxygen consumption decreased from 3.9 +/- 1.1 to 2.9 +/- 0.6 mmol/min (P < 0.05). No significant changes in lower extremity flow and oxygenation variables were found. CONCLUSIONS: The use of dopamine in patients with ALF to increase MAP was associated with increases in systemic and splanchnic oxygen delivery. A concomitant decrease in splanchnic oxygen consumption was observed.

Acute Disease↗
PubMed1999

Blood-brain barrier transport and protein binding of flumazenil and iomazenil in the rat: implications for neuroreceptor studies.

The calculated fraction of receptor ligands available for blood-brain barrier passage in vivo (f(avail)) may differ from in vitro (f(eq)) measurements. This study evaluates the protein-ligand interaction for iomazenil and flumazenil in rats by comparing f(eq) and f(avail). Repeated measurements of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by the double-indicator technique. Cerebral blood flow was measured by intracarotid Xe-injection. The apparent permeability-surface product (PSapp) was measured while CBF or bolus composition was changed. Comparison of PSapp obtained in the absence and presence of 5% albumin in the injectate yielded f(avail), whereas f(eq) was measured by equilibrium dialysis. Iomazenil and flumazenil f(avail) was 62% and 82%, respectively, whereas f(eq) was significantly lower, 42% and 61%. The PSapp for iomazenil and flumazenil increased significantly by 89% and 161% after relative CBF increases of 259% and 201%, respectively. The results demonstrate that application of f(eq) in neuroreceptor studies underestimates the plasma input function to the brain. Model simulations render possible that the differences between f(avail) and f(eq) as well as the effect of CBF on PSapp can be caused by capillary heterogeneity.

Animals↗
PubMed1999

Plasma gelsolin is reduced in trauma patients.

Tissue injury results in the release of the intracellular protein actin which is cleared from the circulation by the plasma proteins gelsolin and Gc-globulin, constituting the Extracellular Actin Scavenger System (EASS). Experimental studies have shown that excessive amounts of actin in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P < 0.0001. There was no correlation between admission levels of gelsolin and ISS or survival. This study illustrates that the plasma concentration of gelsolin is significantly diminished immediately after traumatic injury. Further studies are necessary to establish a role for gelsolin or EASS in the development of MODS in trauma patients. The level of serum or plasma gelsolin can be determined rapidly and accurately using a nephelometric assay.

Adult↗
PubMed1999

Arrhythmogenic right ventricular dysplasia in an American Indian woman.

Arrhythmogenic right ventricular (RV) dysplasia consists of a dilatation of the right ventricle with a reduction of RV ejection fraction with fibrofatty replacement of the RV myocardium in the face of a well-preserved left ventricular systolic function. Arrhythmogenic RV dysplasia, which is a cause of sudden unexpected death, has been reported from many geographic areas, including the United States, Europe, and the Far East. This case report presents the first case of arrhythmogenic RV dysplasia in an American Indian (Native American) patient.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed1999

Highly sensitive methods for quantitation of human immunodeficiency virus type 1 RNA from plasma, cells, and tissues.

Precise and sensitive quantitation of viral RNA in specimens from human immunodeficiency virus (HIV) type 1 (HIV-1)-infected individuals has become an indispensable tool for the monitoring of the efficacy of highly active antiretroviral combination therapy. The present report describes reproducible and efficient protocols with enhanced sensitivity for quantitation of HIV-1 RNA from plasma, peripheral blood mononuclear cells, and tissues with Qiagen silica columns for RNA purification combined with the Roche Amplicor HIV-1 Monitor test for quantitative reverse transcription-PCR (RT-PCR). Extraction of RNA from 0.5 ml of plasma resulted in the detection of fewer than 20 HIV RNA copies/ml of plasma, equivalent to the centrifugation-based boosted RT-PCR assay. Silica extraction of cellular RNA resulted in the detection of fewer than 3 HIV-1 RNA copies/microg of total RNA. These techniques facilitate direct comparisons of viral loads between liquid and cellular specimens. Application of these sensitive methods may improve the assessment of the response to new antiretroviral regimens.

DNA Transposable Elements↗
PubMed1999

Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver.

Lipopolysaccharide (LPS) initiates cholestasis. Whether this process is mediated by tumor necrosis factor-alpha (TNF-alpha) and whether the cholestatic response to LPS is associated with intrahepatic accumulation of possibly toxic substances are under debate. To study these questions the hepatic uptake and biliary excretion of indocyanine green (ICG) was examined in the isolated perfused rat liver 18 h after intravenous treatment of rats with either saline, 1 mg/kg body wt LPS, or LPS and intraperitoneal pentoxifylline (POF) (n = 6 in each group). POF inhibits TNF-alpha release after LPS administration. LPS induced a typical acute-phase response with increased mRNA for acute-phase proteins, reduced albumin mRNA, and increased hepatic uptake of alanine. Intrinsic hepatic clearance of ICG in controls (1.01 +/- 0.05 ml. min(-1). g liver(-1)) was similarly decreased by LPS alone (0.62 +/- 0.04 ml. min(-1). g(-1); P = 0.002 vs. control) or combined with POF (0.66 +/- 0.06 ml. min(-1). g(-1)). A kinetic analysis indicated that LPS reduced both uptake and excretion processes in a balanced manner, so that intrahepatic ICG content was unaffected or even slightly reduced, as confirmed by measurement of ICG contents in the perfused livers. In livers from parallel-treated nonperfused rats, mRNA for the organic anion transporting protein-1 (Oatp1, which is likely to mediate ICG uptake) was unaffected by LPS, whereas the concentration of Oatp1 protein was reduced. Thus LPS induced an acute-phase response that included downregulation of ICG uptake by reduction of Oatp1 protein concentration, possibly at a posttranscriptional level. TNF-alpha appears not to be the mediator because POF did not modify these LPS effects.

Alanine↗
PubMed1998

Hepatic plasma flow estimated according to Fick's principle in patients with hepatic encephalopathy: evaluation of indocyanine green and D-sorbitol as test substances.

The magnitude of hepatic plasma flow in patients with liver failure and hepatic encephalopathy (HE) is unknown because a reliable flow estimate has not been available. The purpose of this study was to estimate hepatic plasma flow in patients with HE and to evaluate indocyanine green (ICG) and sorbitol as test compounds. Fourteen patients with acute liver failure (ALF) and nine patients with chronic liver failure (CLF), all with HE grade II or more, were studied. After hepatic vein catheterization, hepatic plasma flow was estimated by use of constant infusion, simultaneous arterial and hepatic vein concentration measurements, and calculated according to Fick's principle. The hepatic extraction fraction of D-sorbitol 0.179+/-0.144 (mean+/-SD) was higher than the hepatic extraction fraction of ICG 0.054+/-0.085 (P < .001). The low hepatic extraction fraction of ICG rendered this compound unfit for estimation of hepatic plasma flow in these patients. In contrast, by using D-sorbitol the hepatic plasma flow could be estimated in 21 of 23 patients with a median SD of 8.4% (range, 2.6% to 29%). The D-sorbitol estimated hepatic plasma flow was 1.2+/-0.5 L/min (n = 12) in patients with ALF and 1.4+/-0.9 L/min (n = 9) in patients with CLF. These values are higher than what has been reported in normal subjects and in patients with cirrhosis without HE. An elevated hepatic flow should increase oxygen delivery and may enhance the failing liver's ability to remove substances from the blood. At the same time, hepatic first pass metabolism is reduced. We conclude that an elevated hepatic flow in these patients is of clinical importance.

Adult↗
PubMed1998

Sorbitol as a test substance for measurement of liver plasma flow in humans.

The objective of this study was to evaluate whole-body removal kinetics of sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma flow in humans, and to compare measurements of liver flow by Fick's principle using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg) was given intravenously to 6 controls for determination of sorbitol elimination capacity (SEC) and distribution volume, V(sorb)d. Sorbitol infusion (287 micromol/ min) was given to 17 liver patients and 11 controls. Extrarenal sorbitol clearance (V(sorb)x was calculated as infusion rate (corrected for renal excretion and accumulation in V(sorb)d) divided by arterial concentration. Liver flow (Q(ICG)) was calculated from the ICG infusion and arterial and hepatic venous ICG concentrations by Fick's principle. Average SEC was 73 micromol/min/kg, V(sorb)d was 0.16 L plasma per kilogram, and in vivo V(sorb)d was 3 mmol/L. Renal sorbitol excretion rate was 0.03 to 0.31 of infusion rate. Extrahepatic extrarenal removal was not significantly different from zero but varied considerably. Hepatic extraction fraction of sorbitol, (E(sorb)), measured by liver vein catheterization, was 0.35 to 1.04 (median, 0.86) in cirrhotic patients and 0.90 to 0.98 (0.86) in controls. The requirements for using Cl(sorb)x as an estimate of Q(ICG) was not violated by the data in controls, Cl(sorb)x/Q(ICG) 0.70 to 1.55 [median, 1.08]), whereas there was a systematic underestimation in cirrhotic patients (0.72-1.08 [0.85]). Liver flow calculated by Fick's principle using either sorbitol or ICG agreed well. E(sorb) > E(ICG) in each individual except one. Curvilinear relationship between E(sorb) and E(ICG) was in agreement with different kinetic parameters for sorbitol and ICG, and did not require additional assumption of intrahepatic shunts.

Adult↗
PubMed1998

Pharmacokinetics of troglitazone, a PPAR-gamma agonist, in patients with hepatic insufficiency.

OBJECTIVE: Troglitazone is an agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which has been shown to improve the metabolic control of type 2 diabetes. Troglitazone undergoes hepatic metabolism to an inactive sulphate conjugate and an oxidative quinone metabolite with minor activity. The objective of this study was to compare the pharmacokinetics of troglitazone in patients with hepatic insufficiency and normal subjects. METHODS: Three groups of eight subjects with normal liver function and moderate or severe hepatic impairment (Pugh-Child classification) completed this open study. Subjects received a single 400-mg dose of troglitazone 30 min after breakfast. Plasma concentrations of troglitazone and its metabolites were measured and standard pharmacokinetic parameters derived. RESULTS: A 46% increase in area under the plasma concentration-time curve (AUClast) was observed for troglitazone, together with a 154% increase for the quinone metabolite in the patients with moderate hepatic impairment compared with normal subjects, but these did not reach statistical significance. Corresponding increases of 18% and 53% in the severe group also failed to reach statistical significance. For the sulphate conjugate, the AUClast values for both moderate and severe hepatic impairment were in the order of fourfold higher than those in the normal group. There were reductions in the maximum observed plasma concentration (Cmax) of troglitazone to 61% of the normal group in the severe group for troglitazone, and twofold increases in sulphate metabolite Cmax in the moderate and severe groups. There was an approximately threefold increase in the half-life of the sulphate conjugate in subjects with both moderate and severe impairment of liver function compared with normal individuals. First times to maximum concentrations of troglitazone, its sulphate conjugate and the quinone metabolite were significantly longer in all severely impaired subjects compared with those with normal hepatic function, although the range was wide in all cases. Plasma protein binding was high in all subjects measured (mean unbound fraction range 0.7-5.1%), but there were insufficient samples to compare across groups. CONCLUSION: The formation of metabolites of troglitazone following a single dose is not impaired in the presence of reduced liver function although the capacity to eliminate the metabolites is altered. The clinical significance of the effect of liver disease on the conjugates is not clear.

Adult↗
PubMed1998

Serum Gc-globulin in the early course of multiple trauma.

OBJECTIVES: In patients with multiple trauma, actin released from damaged cells may cause severe circulatory disturbance due to thrombi formation. The aim of this study was to evaluate serum concentrations of the actin scavenger, Gc-globulin, in relation to the severity of injury and outcome. DESIGN: Prospective, longitudinal, observational study. SETTING: Trauma center at a university hospital. PATIENTS: Twelve patients with multiple trauma, consecutively included, according to defined criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum Gc-globulin concentrations were measured at the time of admission and daily thereafter for 1 wk or until death. In all patients, the Gc-globulin concentration was significantly low (p < .0001), and the proportion of Gc-globulin bound to actin was already increased compared with normal values (p < .0001) by the time of hospital arrival. There was an inverse correlation between the mean concentration of serum Gc-globulin in the first week after trauma and the Injury Severity Score (r = -0.72, p < .05). Surviving patients had a significantly (p < .05) higher concentration of serum Gc-globulin in the first week after trauma compared with nonsurvivors. CONCLUSIONS: Serum concentrations of Gc-globulin were significantly low in trauma patients. The reduction took place within 60 mins after injury. Because the normal half-life of Gc-globulin is almost 48 hrs, our observations suggest a marked consumption of Gc-globulin immediately after the trauma. This finding could be the first clinical evidence that Gc-globulin plays a role in the systemic inflammatory response syndrome after trauma. This result is supported by the finding that lack of Gc-globulin was related to nonsurvival and the severity of the trauma.

Actins↗
PubMed1998

AV nodal re-entry tachycardia in elderly patients: clinical presentation and results of radiofrequency catheter ablation therapy.

BACKGROUND: Modification of AV nodal conduction by means of radiofrequency catheter ablation has become the accepted mode of therapy for patients with symptomatic AV nodal re-entry tachycardias (AVN-RT). The published results demonstrate high success rates and a low incidence of severe complications. However, published series have primarily dealt with relatively young patient populations. Little is known about the efficacy and risks of radiofrequency catheter ablation of AVN-RT in the elderly. METHODS: We retrospectively analysed our data of 404 patients who underwent a catheter ablation therapy for AVN-RT between 1992 and June 1997. Nine patients were excluded from further analysis because of presence of more than one tachycardia mechanism. The ablation procedure was performed at the time of the diagnostic electrophysiologic study. RESULTS: The mean age of 395 patients undergoing catheter ablation for AVN-RT was 52.3 years (19-90 years); 85 patients were 65 years old or older. Compared with the younger subgroup, these elderly patients (mean age 70.4 years) more often had organic heart disease (coronary heart disease with or without myocardial infarction 19.3% versus 2.6%; P < 0.02), more often had syncopes or presyncopes with AVN-RT (43.2% versus 29.8%; P < 0.05), had more hospitalisations and emergency treatments because of their symptoms (56.8% versus 39.5%; P < 0.05) although the cycle length of the induced AVN-RT was significantly shorter in the younger patient group (325 ms versus 368 ms; P < 0.001). Slow pathway ablation was performed in 94% of the young and 82% of the elderly (P < 0.001). In 17.5% of the elderly patients versus 6.5% of the young (P < 0.05) the fast pathway approach was chosen as the first therapy or tried after an unsuccessful approach to the slow pathway. The overall success rate (96.8% in the young and 95.3% in the elderly) and the recurrence rate (5.8% in the elderly versus 4.9% in the young) were similar in both patient groups. There were no differences regarding the total procedure of fluoroscopy time, radiation exposure or the incidence of high-degree AV-block necessitating pacemaker implantation (2.3% in the elderly versus 1.6% in the young). CONCLUSIONS: In patients older than 65 years, AVN-RT may lead to severe, sometimes life-threatening symptoms, despite the fact that the tachycardia is not as fast as in younger patients. Radiofrequency catheter ablation can be performed effectively and safely and should be offered to these patients as first-choice therapy.

Aged↗
PubMed1998

Risk Factors for Tachycardia Events Caused by Antiarrhythmic Drugs: Experience From the ESVEM Trial.

BACKGROUND: In the Electrophysiology Study versus Electrocardiographic Monitoring (ESVEM) trial, up to seven antiarrhythmic drugs were randomly assigned to 486 patients with a history of sustained ventricular arrhythmia. At baseline, all the patients had inducible sustained ventricular tachycardia (VT) and had >/=10 premature ventricular beats (PVBs) per hour on 48-hour Holter monitoring. A total of 1,229 drug trials were performed. Antiarrhythmic drugs were discontinued during hospitalization because of ventricular tachyarrhythmias thought to be a proarrhythmic effect of the antiarrhythmic drugs in 96 of 479 patients (20%) who received drugs. Proarrhythmic effects were defined as sustained VT, ventricular fibrillation or arrhythmic death, torsade de pointes, or distinct intolerable worsening of the baseline arrhythmia after at least three doses of the drug. METHODS AND RESULTS: Eighteen baseline characteristics were analyzed for factors that would predict a higher incidence of proarrhythmia. These included type of heart disease, previous myocardial infarction, symptom activity scale, gender, type of arrhythmia, VT/ventricular fibrillation, age, left ventricular ejection fraction (LVEF), PVB frequency, heart rate, QRS duration, and QT interval. Multiple logistic regression analysis identified increased mean PVB frequency (P =.003) and increased heart rate (P =.026) as significant predictors of proarrhythmia. Decreased LVEF (<25%) exhibited only a trend toward significance (P =.073). When proarrhythmia was redefined as sustained VT, cardiac arrest of arrhythmic death, or torsade de pointes (n = 59), PVB frequency (P =.003) and heart rate (P =.034) were still the only significant baseline predictors. CONCLUSIONS: In the ESVEM study, higher PVB frequency and higher heart rate were significant predictors of drug-induced proarrhythmia.

Journal Article↗
PubMed1997

[Who dies of morphine and dextropropoxyphene intoxication? Danish experiences from the period 1979-1992].

We studied deaths following intoxication with dextropropoxyphene (D) and opioids (M) in Denmark 1979-1992 with special reference to the sex, age group, contributory cause of death (secondary diagnosis) and manner of death. Deaths following D increased until 1985 for both sexes, where a total of 46 women and 64 men died. In 1985 the National Board of Health drew public attention to this problem which led to a decrease in these deaths among men, while in women a paradoxical increase in suicides outnumbered a reduction in deaths from intoxication accidents. In 1988 D was assigned to the more restrictive prescription rules of opioids, which further reduced the number of deaths. The reduction of D deaths was followed by a corresponding increase in deaths due to M. However, the demographic characteristics of D and M deaths were not entirely identical: The typical D victim had a history of psychiatric disease or drug/alcohol abuse and committed suicide; the age was 40-59 for women and 20-39 for men. The typical M victim also had a history of psychiatric disease and substance abuse but suicides were less common and the majority occurred in the age group 20-39 in both sexes. Both D and M deaths were rare in persons with a somatic secondary diagnosis. We conclude that these poisonings warrant continued attention, and that a more restrictive prescription practice of D and M to patients at risk is justified.

Adolescent↗
PubMed1997

Characterization of the correlation between ATP-dependent aminophospholipid translocation and Mg2+-ATPase activity in red blood cell membranes.

Pseudosubstrates and inhibitors of ATPases were studied with respect to their capability to modulate the kinetic behavior of Mg2+-ATPase and aminophospholipid translocation in red blood cell ghosts. ATP was substituted by the pseudosubstrates of P-type ATPases acetyl phosphate and p-nitrophenyl phosphate. With both pseudosubstrates, aminophospholipid translocation from the outer to the inner leaflets of resealed erythrocyte ghosts could be observed, although with a significantly decreased velocity compared to that in presence of ATP, both with respect to phosphate hydrolysis and translocation. Similarly, the apparent affinities for the pseudosubstrates were much lower than for ATP. Among the inhibitors studied, suramin acted as a competitive inhibitor of ATP towards both Mg2+-ATPase activity and aminophospholipid translocation. However, the inhibition of translocation occurred at a higher inhibitor concentration than the inhibition of Mg2+-ATPase activity. With elaiophylin, only a partial inhibition of Mg2+-ATPase activity could be detected, but translocation of labeled phosphatidylserine was almost completely abolished. With eosin Y, an almost complete inhibition of both Mg2+-ATPase activity and translocation could be achieved. The observed responses of aminophospholipid translocation to ATPase inhibitors strongly suggest that a P-type ATPase, part of which displays a Mg2+-ATPase activity, is involved in aminophospholipid translocation.

Adenosine Triphosphate↗
PubMed1997

Hepatic ICG removal in the pig depends on plasma protein and hematocrit: evidence of sinusoidal binding disequilibrium and unstirred water layer effects.

The influence of binding protein concentration and hematocrit on hepatic uptake of indocyanine green (ICG) was studied in anesthetized pigs during constant infusion of ICG. By exchange transfusions, we either substituted plasma protein with dextran 70 (n = 8) or changed hematocrit (n = 8). Intrinsic hepatic clearance of ICG, K, was calculated from plasma flow rate and concentrations in peripheral artery and liver vein after correction for extrahepatic distribution. By analyzing the relative change of K versus either the protein dilution factor or the change in plasma volume fraction (1-hct), we evaluated four current models for hepatic uptake of protein-bound substances even though a number of model parameters were unknown (parameter-free testing). Protein dilution factors (unitless) of 0.506 +/- 0.027, 0.673 +/- 0.011, and 0.749 +/- 0.028 were associated with inverse K ratios of 0.621 +/- 0.025, 0.758 +/- 0.021, and 0.817 +/- 0.013. These data rejected the traditional hypothesis that ICG uptake is proportional to the unbound concentration. They were compatible with development of binding disequilibrium along the sinusoidal lumen, an unstirred water layer close to the hepatocyte surface, or facilitated uptake from the bound pool. A plasma volume ratio [(1-hct2)/(1-hct1)] of 1.14 +/- 0.02 was associated with a K ratio of 1.07 +/- 0.02 (P = .01). Only sinusoidal binding disequilibrium predicted this finding, whereas an additional unstirred water layer effect could not be excluded. The observations could be simulated by a model that included both of these effects. Thus, neither the relative changes of K nor the absolute K values required the assumption of facilitated uptake from the bound pool. The parameter-free design presented may be useful with other ligands in intact animals.

Animals↗