Biomedical subjects

P Ott

Publications and source records attributed to P Ott.

At least 73 records · Page 4Linked to original sources

PubMed1997

Reduced serum Gc-globulin concentrations in patients with fulminant hepatic failure: association with multiple organ failure.

OBJECTIVE: To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.

Adolescent↗

PubMed1997

Psychopathology in preadolescent sons of fathers with substance use disorders.

OBJECTIVE: While preadolescent children of parents with substance use disorders (SUDs) are known to have more behavior problems, depression, and anxiety than expected, psychiatric disorders in these children and their relationships with parental disorders have not been systematically investigated. This study compares the psychiatric disorders of preadolescent boys of fathers with and without SUDs and examines the relationships between offspring and parental psychopathology. METHOD: Fathers (i.e., probands) of boys 10 through 12 years old were recruited to represent families of boys with paternal SUD (high risk or HR: n = 113) and boys without paternal SUD (low average risk or LAR: n = 170). These boys (i.e., index cases) and their biological parents participated in structured diagnostic interviews, and diagnoses were determined by the best-estimate method. RESULTS: Disruptive behavior disorders and anxiety disorders were more prevalent in HR than in LAR index cases. Logistic regression analyses examining the relationships between parental and index case psychopathology indicated that parental childhood psychiatric disorders were more strongly predictive of index case psychiatric disorders than parental adulthood psychiatric disorders, including SUDs. CONCLUSIONS: Inasmuch as HR boys had increased rates of disruptive behavior disorders and anxiety disorders, these disorders may be important targets for early intervention to prevent the development of SUD, as well as the morbidity associated with these disorders. Prevention efforts and studies of the transmission of liability for psychiatric disorders in children should carefully consider parental childhood characteristics.

Case-Control Studies↗

PubMed1997

Haemodynamic changes after high-volume plasmapheresis in patients with chronic and acute liver failure.

OBJECTIVE: To evaluate the haemodynamic changes during treatment with high-volume plasmapheresis in patients with chronic liver failure compared to patients with acute liver failure. METHODS: Haemodynamic measurements were performed with a Swan-Ganz catheter and thermodilution technique. High-volume plasmapheresis (mean plasma exchange of 8.6 litres) was performed in 11 patients with chronic and 16 patients with acute liver failure. RESULTS: In patients with chronic liver failure, systemic vascular resistance index was unaltered: 1193 +/- 494 dynscm-5m2 before treatment versus 1180 +/- 399 dynscm-5m2 after. Mean arterial pressure increased from 69 +/- 11 mmHg to 78 +/- 13 mmHg (P < 0.05) and cardiac output increased from 8.1 +/- 2.4 l/min to 8.9 +/- 2.4 l/min (P < 0.05) during high-volume plasmapheresis. In patients with acute liver failure, systemic vascular resistance index increased from 1154 +/- 628 dynscm-5m2 to 1614 +/- 738 dynscm-5m2 (P < 0.001). In this group mean arterial pressure increased from 78 +/- 16 mmHg to 95 +/- 10 mmHg (P < 0.001) and cardiac output decreased from 9.6 +/- 3.7 l/min to 8.2 +/- 2.9 l/min (P < 0.01). CONCLUSION: The hyperkinetic circulation in chronic and acute patients was differently affected by high-volume plasmapheresis. We suggest that in chronic liver failure both portosystemic shunting and chronic peripheral vasodilation may contribute to the hyperkinetic syndrome, whereas in acute liver failure a humoral factor which can be removed by high-volume plasmapheresis is a main contributor.

Acute Disease↗

PubMed1997

Effect of ventricular dilatation on defibrillation threshold in the isolated perfused rabbit heart.

INTRODUCTION: Ventricular dilatation has important electrophysiologic effects, but its effect on ventricular defibrillation threshold (DFT) is unknown. METHODS AND RESULTS: A fluid-filled, latex balloon was placed in the left ventricular cavity of 19 isolated rabbit hearts. In each experiment, an undilated volume (equivalent to a left ventricular end-diastolic pressure of approximately 0 mmHg) was compared to a dilated volume achieved by adding 1.0 mL of saline (n = 10) or 5% dextrose (n = 9) to the intracavitary balloon. Left ventricular effective refractory period (ERP) and DFT were determined at each volume. Defibrillation was attempted with a monophasic shock delivered between a patch electrode positioned over the posterior left ventricle (cathode) and a metallic aortic cannula (anode). DFT was determined using a modified "down/up" protocol with 10 V steps. Ventricular dilatation increased the left ventricular end-diastolic pressure from 0 +/- 0.5 mmHg to 35 +/- 3 mmHg (P < 0.001), decreased the average left ventricular ERP 15% (from 116 +/- 3 msec to 99 +/- 3 msec; P < 0.001), and increased the average DFT 30% (from 96 +/- 4 V to 125 +/- 7 V; P < 0.001). In one third of experiments, the dilated DFT was > or = 150% of the DFT at zero volume. The mechanism of the observed increase in DFT is unknown but may be related to the decrease in refractoriness observed with ventricular dilatation. CONCLUSION: Acute ventricular dilatation in this model increased DFT an average of 30%, an effect not previously described. This observation may have implications for patients with implantable cardioverter defibrillators.

Animals↗

PubMed1997

Nontraditional effects of protein binding and hematocrit on uptake of indocyanine green by perfused rat liver.

We used a novel parameter-free approach to study the role of protein binding in the hepatic clearance of indocyanine green (ICG) from reconstituted pig blood by perfused rat liver. Either perfusate total plasma protein concentration or hematocrit was changed. By analyzing protein concentration ratios or plasma volume ratios relative to ratios of intrinsic hepatic clearance of ICG (K), it was possible to evaluate current models of hepatic uptake of protein-bound ligands without precise knowledge of some of the model parameters. A four-fold increase in the total plasma protein concentration produced only a 36% decrease in K. This was substantially less than predicted by the traditional model, where K is proportional to the free concentration of ligand. Because an unstirred water layer effect could not by itself account for the observations, the effects of binding disequilibrium in the sinusoids or uptake directly from the bound pool had to be considered. To discriminate, hematocrit was increased from 15% to 29%, causing a 20% decrease in the sinusoidal plasma volume. A significant reduction in K strongly suggested a sinusoidal binding disequilibrium effect. The dissociation rate constant predicted by this model was confirmed by in vitro measurement, further supporting this interpretation. The simple experimental design and its parameter-free evaluation provide a new tool for investigating the hepatic uptake of protein-bound ligands.

Animals↗

PubMed1997

The effect of cimetidine on ethanol concentrations in fasting women and men after two different doses of alcohol.

BACKGROUND: Serum ethanol concentrations may become higher when alcohol is consumed during treatment with histamine receptor antagonists, especially if ethanol is ingested postprandially. Only a few studies have investigated fasting subjects, and women have only been investigated sporadically. METHODS: The present study compared serum ethanol concentrations after a 4-h fast followed by a low (0.15 g/kg) and a high (0.45 g/kg) dose of ethanol, on two separate occasions in six women and six men. The study was carried out before and after treatment with 400 mg cimetidine twice daily. RESULTS: Cimetidine administration did not change the area under the concentration-time curve or the maximal serum ethanol concentration in either women or men, irrespective of ethanol dose. Ethanol elimination rate was unchanged by cimetidine. CONCLUSION: Cimetidine does not influence the ethanol concentration-time curve when ethanol is ingested on an empty stomach.

Adult↗

PubMed1997

Reduced gastric emptying and mesenteric blood flow in IDDM with cardiac autonomic neuropathy.

Our objective was to investigate the relationship between gastric emptying and mesenteric blood flow in type 1 diabetic patients with (CAN+) and without (CAN-) cardiac autonomic neuropathy. CAN was determined by a series of cardiovascular reflex tests and power spectral analysis of heart rate variations (HRV) using a computerized system. We calculated from these data a score for cardiac autonomic neuropathy with a maximum of 7 points (1 point for abnormal value of: CV of HRV at supine rest, CV of HRV during deep breathing, Valsalva ratio, lying-to-standing ratio, PSA of HRV in the low frequency band, PSA of HRV in the mid frequency band, blood pressure response to standing). Patients were considered to have CAN if at least 3 of the 7 parameters were found to be abnormal (CAN score > or = 3). The resulting groups (CAN-, n = 14 vs. CAN+, n = 16) were well matched with respect to age (53 +/- 11 vs. 51 +/- 12 years), BMI (27.2 +/- 3.3 vs. 25.9 +/- 3.6 kg/m2), duration of diabetes (162 +/- 157 vs. 158 +/- 100 months), fasting blood glucose (6.9 +/- 2.6 vs. 6.8 +/- 2.4 mmol/l) and HbA1c (7.2 +/- 1.5 vs. 7.3 +/- 2.0%). Gastric emptying was determined by real-time ultrasonography (antral planimetry) during 60 min after a semiliquid test meal (Fresubin diabetes 300 ml, 53% carbohydrate, 32% lipid, 15% protein) and the blood flow of the superior mesenteric artery was measured by Doppler ultrasound technique. Type I diabetic patients with CAN had a significantly higher CAN score than those without CAN (6.1 +/- 0.4 vs. 1.3 +/- 0.7). Mean preprandial (before ingestion of the test meal) as well as postprandial (immediately after ingestion of test meal) antral areas of CAN+ (5.2 +/- 2.0v/10.9 +/- 2.8 cm2) and CAN- (5.1 +/- 1.5/10.8 +/- 2.2 cm2) were comparable. CAN+ had significantly slower decrease of postprandial antral areas at 15, 30, 45 and 60 min after ingestion of test meal (-1.7 +/- 0.4/-8.3 +/- 1.2/-9.5 +/- 0.9/-19.5 +/- 2.0 delta % compared to postprandial value) compared to CAN- (-8.9 +/- 1.8/-22.5 +/- 2.6/-29.1 +/- 2.9/-35.5 +/- 2.9 delta %). The increase in mesenteric blood flow at 15, 30 and 45 min after the meal was significantly reduced in CAN+ compared to CAN- patients. Significantly negative correlations were found between the CAN score and the decrease of antral area as well as between CAN score and the increase of diastolic mesenteric blood flow and significantly positive correlations between the decrease of antral area and the increase of diastolic mesenteric blood flow. In conclusion, type 1 diabetic patients with cardiac autonomic neuropathy showed delayed gastric emptying and diminished mesenteric blood flow during 60 min after ingestion of a semiliquid test meal.

Adult↗

PubMed1996

[Recommendations for treatment of paracetamol poisoning. Danish Medical Society, Study of the Liver].

Based on recent reports concerning the efficacy of N-acetylcysteine (NAC) in paracetamol (acetaminophen) poisoning, guidelines for treatment and control of these patients are reviewed by a study group under the Danish Association for the Study of the Liver. It is recommended that NAC-treatment is initiated immediately after referral and continued for 36 hours in all cases. Further NAC-treatment should not be discontinued before a decrease in INR has been observed.

Acetaminophen↗

PubMed1996

Phospholipid asymmetry in red blood cells and spectrin-free vesicles during prolonged storage.

Erythrocytes and spectrin-free DMPC-induced vesicles released from the cells were incubated for 3 weeks at 6 degrees C under conditions of metabolic ATP-depletion. Phosphatidylserine (PS) asymmetry was monitored during this period by use of the prothrombinase assay. Prothrombinase activities measured at the beginning of the incubation period indicated that approximately 0.06% of PS was located at the outer layer of the red cell membrane, whereas in DMPC-induced vesicles approximately 1.5% the PS was exposed on the outside. After completion of the incubation period PS exposure on the outside of red cells and vesicles was increased by no more than 5-fold. On the other hand, with vesicles prepared with a significantly increased (4-fold) ATP-content to sustain translocase activity, the incubation process resulted in a surprisingly high (20-fold) increase of PS exposure. With vanadate, an inhibitor of the aminophospholipid translocase, included in the incubation medium, the redistribution of PS was even more pronounced. These observations indicate that PS asymmetry in spectrin-free vesicles can not be directly correlated to either ATP content or translocase activity and suggest that besides the aminophospholipid translocase and the membrane skeleton, other mechanisms must be involved in maintaining phospholipid asymmetry.

Adenosine Triphosphate↗

PubMed1996

Admission levels of serum Gc-globulin: predictive value in fulminant hepatic failure.

Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P < .001), whereas the complex ratio in nonsurvivors did not differ significantly from that of survivors. Gc-globulin levels were significantly lower in 59 patients with non-acetaminophen-induced FHF, compared with 18 patients with acetaminophen-induced FHF (P < .01). Using a cutoff level of serum Gc-globulin of 100 mg/L, a lesser value correctly predicted nonsurvival in 79 percent of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly predicted nonsurvival and survival in 69 percent and 57 percent, respectively, of the same non-acetaminophen-induced FHF patients and in 60 percent and 38 percent, respectively, of the acetaminophen-induced FHF patients. Thus, in our study population, the predictive properties of Gc-globulin were in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L.

Acetaminophen↗

PubMed1996

The kinetics of continuously infused indocyanine green in the pig.

Indocyanine green (ICG) is used in cardiology and hepatology for the estimation of cardiac output, liver function, and splanchnic blood flow. ICG is bound to plasma proteins and ultimately excreted by the liver. We studied the whole body kinetics of ICG during constant infusion in pigs weighing 30-40 kg. The conventional kinetic model (backflux model) assumes that deviations from one-compartmental linear kinetics is caused by backflux from a liver storage to plasma, and that no extravascular, extrahepatic distribution takes place. This model was tested against an alternative (redistribution) model postulating that temporary redistribution of ICG into an extrahepatic extravascular storage was responsible for the deviations while the hepatic uptake was a one-way first-order process. A mathematical analysis of the two models showed that they predicted different time courses of the hepatic extraction fraction of ICG. Thus, with blood sampling from both a peripheral artery and a hepatic vein, a discriminative model-testing experiment was possible. This test required a first-order steady-state hepatic removal of ICG which was confirmed in 7 experiments with infusion rates varied in a stepwise fashion (0.133 +/- 0.003, 0.269 +/- 0.010, 0.547 +/- 0.020 and 0.130 +/- 0.003 mumol.min-1). In the model-testing experiments (n = 10) ICG was infused at a constant rate of 0.135 +/- 0.07 mumol.min-1. The mean concentration in peripheral artery (microM) was well fitted by the biexponential function C(t) = 0.476.(1-0.632.e-0.216.1-0.368.e-0.0172.1). The time course of the observed hepatic extraction fraction was significantly different (p = 0.004) from that predicted from the backflux model but in agreement (p = 0.98) with the new model assuming hepatic removal to be a one-way process and implying temporary ICG redistribution into an extrahepatic, extravascular storage with an apparent volume of 0.144 +/- 0.023 L.Kg-1. Accordingly, extravascular ICG was demonstrated in a number of different tissues after 4-hr infusion (n = 3). If ICG is used to estimate hepatic blood flow according to Fick's principle, the use of a backflux model to correct for non-steady-state conditions will lead to an overestimation of hepatic blood flow of 28% after 25-min infusion, 16% after 50 min, and 6% after 100 min. The study indicated that distribution of ICG between plasma and tissues is not instantaneous, and that the time course of the redistribution itself significantly influences whole body kinetics. Comparison with a previously published study by Ott, Keiding, and Bass of ICG kinetics after bolus injection suggested that a two-compartment model was insufficient and that the kinetics for the exchange of ICG between plasma and the redistribution space may be nonlinear. The study demonstrates how blood sampling on both sides of the eliminating organ can expose the influence of redistribution. The discriminative model test for constant infusion experiments is novel and may be useful with other ligands.

Albumins↗

PubMed1996

The Role of Digoxin in the Treatment of Chronic Congestive Heart Failure.

It is now well established that digoxin is an effective drug for the treatment of heart failure. Since treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality in congestive heart failure, digoxin should be added to ACE inhibitors in patients with moderate or severe heart failure. The beneficial effects of digoxin may be due, in part, to its well-documented sympathoinhibitory effects that can avert the adverse effects of long-term excessive sympathetic adrenergic stimulation in heart failure.

Journal Article↗

PubMed1995

[Poisoning by green and white mushrooms at a special hepatology unit, 1989-1994].

In the period 1989-1994 eight patients, who were intoxicated with the mushrooms Amanita phalloides (death cap) or Amanita virosa (deadly agaric) were treated at a Department of Hepatology. All patients had had a symptom free period of more than eight hours before the onset of gastrointestinal symptoms; these symptoms lasting in many cases for several days. All patients had biochemical signs of hepatocellular damage and three patients developed hepatic encephalopathy, fulfilling the criteria for fulminant hepatic failure (FHF). Two died and one patient underwent successful urgent liver transplantation. ALL FHF patients had a prothrombin index below 10% and increased creatine. Antidote treatment with penicillin and silibinine should be given promptly on suspicion of Amanita intoxication and should not await biochemical parameters. Transferral to a hepatological department with access to liver transplantation should be considered if abnormal biochemical liver function develops.

Adult↗

PubMed1995

[Paracetamol poisoning at a department of hepatology].

In this retrospective study we evaluated the frequency of complications in 108 patients with acetaminophen poisoning admitted to the Department of Hepatology, Rigshospitalet, Copenhagen from 1.10.1990-30.9.1993. Twenty-five patients (23%) developed hepatic encephalopathy grade II-IV, with a survival rate of 44%. In patients who developed grade IV encephalopathy the median time from intoxication to INR > 3.7 was 60 hours. At a median of only five hours later grade II encephalopathy was present, and grade IV at a median of a further 20 hours later. Ninety-three patients were re-evaluated according to the nomogram indicated by Prescott (6). If the initial position was in the "very severe" area the risk of developing encephalopathy was 34% (20-51%), if not the risk was 6% (1-16%). Serum creatinine above 200 microM at admission indicated a risk of hepatic encephalopathy of 64% (35-87%). INR > 1.54 was associated with a 35% risk of hepatic encephalopathy. Patients in the "very severe" area should be referred to a unit where liver transplantation is possible, even if other factors known to indicate poor prognosis are not present.

Acetaminophen↗

PubMed1995

[Poisonings due to analgesics during a period of 14 years in Denmark--a registry study of the period 1979-1992].

The study describes consumption of and poisoning by analgesic drugs in Denmark during the period 1979-1992. During this period, fatal poisonings from analgesics almost doubled to 200 deaths per year (40% of all drug related deaths in Denmark). The annual consumption of opioids increased at the beginning of the period, but during 1985-1992 it was relatively constant at 20 million defined daily doses (DDD) and associated with 600 hospital admissions and 150-170 deaths due to poisoning per year. Within the opioid group dextropropoxyphene consumption and poisonings decreased following a National Board of Health initiative in 1985-1987. As for the weak analgesics, consisting mainly of paracetamol or salicylates, the total consumption increased gradually and reached 145 million DDD in 1992, corresponding to 160 tablets per inhabitant per year. This consumption was associated with approximately 750 hospital admissions and 40 deaths due to poisoning. As judged from the mortality per dose the weak analgesics are 20-30 times safer than the opioids.

Analgesics↗

PubMed1995

Band 3 Chur: a variant associated with band 3-deficient hereditary spherocytosis and substitution in a highly conserved position of transmembrane segment 11.

We studied a large Swiss family with dominantly inherited hereditary spherocytosis and band 3 (anion exchanger 1, AE1) deficiency. Band 3 cDNA was analysed by single-strand conformation polymorphism analysis and nucleotide sequencing. A new point mutation was found: G771D (GGC-->GAC). This change was present in all eight investigated patients but absent in four healthy members of the family. It is located at a highly conserved position in the middle of transmembrane segment 11, introducing a negative charge in a stretch of 16 apolar or neutral residues. None of the six amino-acid substitutions already known in this region as being associated with band 3 deficiency were recorded. To rule out any major transcriptional or post-transcriptional defect, we evaluated the amount of band 3 mRNA by RNase mapping using a band 3-protein 4.1 chimaeric probe. Similar mRNA amounts were present in patients and controls. Our results strengthen the view that some amino-acids, that are well conserved throughout the AE family, may be crucial for the insertion and/or the stabilization of band 3 within the lipid bilayer. At the present time, most of the mutations altering such residues are located in the C-terminal region of band 3.

Animals↗

PubMed1995

Tachycardia-induced cardiomyopathy in a cardiac transplant recipient: treatment with radiofrequency catheter ablation.

INTRODUCTION: Two years after orthotopic cardiac transplantation, a 60-year-old man presented with unexplained congestive heart failure and an incessant atrial tachycardia. METHODS AND RESULTS: Electrophysiologic evaluation identified the underlying arrhythmia as automatic atrial tachycardia with site of origin at the high anterior lateral right atrial wall. Radiofrequency catheter ablation successfully eliminated the tachycardia, which resulted in prompt improvement of this patient's congestive heart failure. CONCLUSION: This is the first reported case of tachycardia-induced cardiomyopathy in a cardiac transplant patient. Radiofrequency catheter ablation can be used successfully in this patient population.

Bundle of His↗

PubMed1994

Hereditary spherocytosis associated with protein band 3 defect in a Swiss kindred.

A kindred with hereditary spherocytosis, in which 10 individuals were affected, was investigated. Gel electrophoresis of membrane proteins revealed a protein band 3 defect (densitometric reduction 14.4 +/- 7.0%). The erythrocyte morphology of unsplenectomized patients showed so-called pincered erythrocytes (about 1%), which were not present in the five splenectomized patients. Splenectomy also reduced anisocytosis and all parameters of haemolysis, while haemoglobin increased. The osmotic resistance was reduced in patients with protein band 3 deficiency. Erythrocyte filterability through 3 microns pores was decreased. A significant correlation was found between osmotic resistance and filterability. The membrane elastic modulus of erythrocytes was not affected. These results on structural and functional properties of protein band 3 deficient erythrocytes may contribute to a better understanding of this newly discovered form of hereditary spherocytosis.

Adolescent↗