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Biomedical subjects

H Lange

Publications and source records attributed to H Lange.

At least 109 records · Page 6Linked to original sources

The role of membrane contact in hemodialysis-induced granulocyte activation.

Besides complement, interleukin-1 and beta 2-microglobulin, activation of granulocyte function has been found out to be the major parameter in the determination of dialyzer biocompatibility. Unfortunately, the term 'granulocyte activation' has been widely used without restriction to distinct functions or definition of the related metabolic pathways. Therefore, the present study aims to elucidate the influence of hemodialysis (HD) pure membrane contact on granulocyte O2- release. The activation of this metabolic pathway which is also known as the so-called oxidative burst has been generally accepted as the initial signal in the granulocyte inflammatory activation cascade. Two membranes which have been previously shown to differ most widely in biocompatibility, cuprophane and polysulfone, have been selected. During HD with cuprophane the stimulatable O2- release was initially decreased, whereas polysulfone HD was effectless on granulocyte oxidative metabolism. The inhibition was due to a prestimulation of the granulocyte by pure interaction of the cell with the surface of the dialyzer membrane which could be proved by evaluating a plasma-free model. Activation of oxidative metabolism was strongly correlated with granulocyte adherence, showing a significantly higher rate of cell adherence in the case of cuprophane. Nevertheless, sheer forces were able to prevent granulocytes becoming adherent directly to the dialyzer membrane, but sheer forces were not able to influence the oxidative burst reaction, suggesting that the membrane-related stimulation of oxidative metabolism occurs immediately after a very short, possibly a single and hasty contact of the cell to the surface of the dialyzer membrane.

Aged↗

Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex.

Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.

Acute Kidney Injury↗

[Ion-selective electro-analyser with tubular solid contact flow-through sensors for continuous bioelectrochemically controlled hemodialysis of K+, Na+, Ca2+, Cl- and pH].

An ion-selective electroanalyzer for bio-electrochemically controlled hemodialysis will be described. The bedside analysers are solid-contact flow-through electrodes based on tubular carrier-PVC-membranes for potassium, sodium, calcium and chloride. This multi-measurement system with series-connected biosensors in modular construction is provided with a chemosensor for pH measurements. Besides the technical aspects of the apparatus, the quantitative electrode characteristics and the fundamental basis for the application of ion activities in clinical analytic measurement will be described.

Acid-Base Equilibrium↗

Biologically active recombinant prothrombin and antithrombin III expressed in a human hepatoma/vaccinia virus system.

Several systems have been devised that are based on viral promoters suitable for gene expression in eukaryotic cells. One such system, vaccinia virus, has been successfully used to express a variety of heterologous proteins following the construction of a recombinant virus. Indeed, because of the ability of vaccinia virus to infect a wide range of host cells, the expression system can be custom-designed so that a cell line can be instrumental in ensuring the correct processing of the recombinant polypeptide. We show that recombinant vaccinia virus and human hepatoma cells in culture are an efficient expression system with which to produce correctly modified and biologically active human prothrombin (15 micrograms/10(7) cells) and antithrombin III (40 micrograms/10(7) cells).

Animals↗

Fluid-shift during computer-modulated profile hemodialysis (CMP-HD).

Computer-modulated profile hemodialysis was examined for patients' comfort and fluid-shift. Fifteen patients were studied after two weeks of dialysis with each of the following profiles: A): constant ultrafiltration (UF) and dialysate sodium (138 mmol/l); B): decreasing UF; C): decreasing UF and decreasing high dialysate sodium (starting 10% above serum-sodium, with a gradual reduction to 138 mmol/l in the fourth hour). Patients with a calculated increase of intracellular volume (ICV) during dialysis had more complaints after dialysis than the others. ICV decreased in all patients with low serum-sodium (less than 136 mmol/l) during all profiles, whereas in patients with higher sodium, only profile C led to a decrease of ICV. However, interdialytic weight gain increased about 75% in patients with low serum-sodium under profile C. The sodium profile could help in preventing imbalance without side effects in patients with high sodium.

Aged↗

[Mean equipotent blood pressure-lowering concentrations of halothane, isoflurane and enflurane during balanced anesthesia differ from conventional MAC-values].

Balanced anesthesia is a technique that allows control of blood pressure in patients with coronary artery disease. In order to evaluate the relative requirements of volatile anesthetics during basic opioid analgesia, 51 patients with unimpaired left ventricular function who were undergoing coronary artery bypass grafting during balanced anesthesia were investigated. They were randomly assigned to three groups, i.e. halothane (H), isoflurane (I), and enflurane (E). Permanent medications were maintained up to 12 h preoperatively. After premedication with flunitrazepam, promethazine and piritramide, anesthesia was induced with 7 micrograms/kg fentanyl, 0.3 mg/kg etomidate, and 0.1 mg/kg pancuronium and continued with fentanyl infusion (0.1 microgram/kg-1 min-1). Volatile anesthetics were applied in oxygen/air and adjusted to keep the mean arterial blood pressure within +/- 20% of the preoperative value. End-expiratory concentrations of volatile anesthetics were measured (Capnomac, DATEX) and averaged over time. The mean ages of the patients in the different groups were 60 +/- 7.6 years (H), 59 +/- 7.1 years (I), and 60 +/- 6.9 years (E). Four patients in the halothane group, six in the isoflurane group, and five in the enflurane group took beta-blockers preoperatively. The cumulative doses of fentanyl were: H = 0.80 +/- 0.17 mg, I = 0.85 +/- 0.16 mg, and E = 0.83 +/- 0.16 mg at the time of skin incision and H = 1.20 +/- 0.26 mg, I = 1.38 +/- 0.19 mg, and E = 1.24 +/- 0.25 mg at the beginning of extracorporeal circulation.2+ which are possibly the reason for the high O2-MAC value, which may be abolished during balanced anesthesia. However, both the negative inotropic and the vasodilatory effects of enflurane are more likely explanations for the results. It is concluded that 0.5 to 1.0 MAC of halothane, isoflurane, or enflurane used as equipotent components of balanced anesthesia for blood pressure control during aorto-coronary bypass grafting may differ considerably from the conventional MAC concept.

Aged↗

[Differential diagnosis of transplant function disorders in therapy with monoclonal antibodies OKT3].

The use of OKT3 monoclonal antibodies has improved the immunosuppressive therapy. Due to the high efficiency of this treatment there is an increased risk of overimmunosuppression and occurrence of life-threatening viral infections. Therefore a cautious application of OKT3 is mandatory, a reliable differential diagnosis of the deteriorating graft function essential. In this study the high diagnostic value of urinary neopterin in the early and reliable diagnosis of CMV infection under OKT3 therapy in contrast to serum amyloid A as a marker of rejection could be shown. A differential therapy, supporting or reducing the immunosuppression, might be facilitated by daily monitoring of the neopterin and serum amyloid A.

Adult↗

Changes in cardiac output determined by continuous-wave Doppler echocardiography during propafenone or mexiletine drug testing.

Antiarrhythmic drugs may induce congestive heart failure in patients with malignant ventricular arrhythmias and depressed left ventricular (LV) function. Whether Doppler echocardiography can detect drug-induced depression in LV function was assessed. Continuous-wave Doppler measurements of ascending aortic blood flow velocity were obtained in 16 patients while not receiving antiarrhythmic drugs on 2 consecutive days to assess day-to-day variability, as well as while receiving maximally tolerated oral doses of mexiletine (11 patients) and propafenone (9 patients). While receiving propafenone, a drug with moderate negative inotropic activity, peak flow velocity declined by 9 +/- 8% (p less than 0.05), the flow velocity integral (termed stroke distance, representing stroke volume) declined by 8 +/- 11% (p less than 0.10), the rate-corrected stroke distance declined by 9 +/- 8% (p less than 0.02) and the minute distance, representing cardiac output, declined by 10 +/- 12% (p less than 0.05). In contrast, while receiving mexiletine, a drug with minimal negative inotropic activity, none of these parameters changed significantly. Five of 9 patients (56%) treated with propafenone showed a decline in rate-corrected stroke distance exceeding the 95% confidence limit of day-to-day variability, which was +/- 13 percent. Two of these 5 patients developed clinical signs of congestive heart failure. Continuous-wave Doppler echocardiography can detect antiarrhythmic drug-induced LV dysfunction and may be used to anticipate the development of significant clinically overt congestive heart failure.

Cardiac Output↗

Latent inhibition of granulocyte function by cyclosporine A.

According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages.

Adult↗

Hepatic and extrahepatic disposition of propofol in patients undergoing coronary bypass surgery.

In order to clarify the relative contribution of the liver to the short term disposition of propofol, hepatic blood flow was measured during induction of anaesthesia with an i.v. bolus dose of propofol 2 mg kg-1. Total clearance of the drug was 2390 (SD 340) ml min-1, hepatic extraction 82% and hepatic clearance 1060 (260) ml min-1. During the 60-min period of observation, hepatic extraction of propofol increased from 79% to 92%. It is concluded that, within 1 h, only 44% of the administered dose is removed by the liver. Consequently, drug accumulation may occur with repeated dosing or infusion of propofol. The increase in extraction results presumably from slow release of propofol from the soy-bean emulsion.

Adult↗

Influence of computer-modulated profile haemodialysis on cardiac arrhythmias.

To reduce hamodialysis-induced ventricular arrhythmias, each of 15 patients (age 66.9 +/- 6.2 years) with end-stage renal disease and cardiac irregularities was treated subsequently with four different computer-modulated bicarbonate haemodialysis profiles (A-D) for 2 weeks respectively: (A) constant UF, dialysate Na (138 mmol/l) and K (2 mmol/l); (B) decreasing UF, otherwise as (A); (C) decreasing UF and Na (starting with 10% higher than serum Na), otherwise as (A); (D) decreasing UF and Na, adapted K to achieve a maximal reduction of serum K of only 15%/h. Cardiac monitoring was done by 11 h ECG. Only in haemodialysis profile D a distinct reduction of ventricular extrasystoles during and after haemodialysis was obtained. It was accompanied by an improvement in the Lown classification. In addition, a weak but highly predictive correlation between the number of ventricular extrasystoles in the last hour of dialysis and the difference between pre- and post-dialysis potassium concentration in the serum could be established (r = 0.37; P less than 0.004). Computer-modulated potassium profile haemodialysis is a useful tool to reduce the number and severity of ventricular extrasystoles.

Aged↗

Kinetics of pulmonary leukocyte sequestration in man during hemodialysis with different membrane-types.

Although it has been suggested that pulmonary sequestration of leukocytes could account for membrane-dependent white blood cell depletion in HD, direct evidence in patients is still lacking. Therefore a study was initiated to test whether and how leukocytes distribute in the lung circulation during HD with different membranes. Thirteen patients suffering from chronic renal failure underwent lung scintigraphy during HD with cuprophane (n = 3), hemophane (n = 8) and polysulfone (n = 2) lowflux capillary dialyzers. Isolated autologous leukocytes were labelled with 99m-Technetium and reinfused before starting HD. Distribution of leukocyte related activity was registered by lung scintigraphy. In comparison to normal lung scintigraphy performed without HD, an impressive redistribution peak was demonstrated 10-20 min after the start of HD with cuprophane and also to a lesser extent with hemophane. When HD was performed with polysulfone the decrease in activity was delayed but no real redistribution was obtained. In accordance with other phenomena, such as peripheral leukopenia and changes in granulocyte oxidative metabolism, pulmonary sequestration of leukocytes takes place in man in the initial phase of HD and appears to be strongly dependent on the type of membrane.

Humans↗

[Propofol infusion for sedation in regional anesthesia. A comparison with midazolam].

50 non-premedicated ASA class I or II patients were allocated randomly into two groups and received either a variable infusion of propofol or midazolam for sedation during orthopaedic surgery with regional blockade. To achieve a well-sedated patient with eyes closed and able to follow commands, the dose requirements for propofol were 1.25 mg/kg +/- 0.5 as a loading dose followed by a mean infusion rate of 3.17 mg kg-1 h-1 +/- 1.4 and for midazolam 0.073 mg/kg +/-0.02 and 0.074 mg kg-1 h-1 +/- 0.14. Steady-state plasma concentrations of propofol averaged 1.23 micrograms/kg +/- 0.75 and of midazolam 134 ng/ml +/- 62. Recovery was significantly shorter for propofol: 3.42 +/- 2.5 versus 8.05 min +/6.2 for midazolam. Perioperative cooperation was similar in both groups providing good or excellent conditions in 76% with propofol and in 52% with midazolam. 2h after discontinuation of the infusion 92% of the propofol patients were alert, while 36% of the midazolam were sleeping again. Cardiovascular effects of both drugs were minimal; however significant respiratory depression and/or airway obstruction developed in both groups (propofol 48%, midazolam 52%) requiring therapeutic intervention. Additional undesirable effects were: severe cough (propofol 40%, midazolam 20%), inadvertent movements (propofol 36%, midazolam 24%), confusion (propofol 24%, midazolam 20%), euphoria (propofol 44%), pain on injection (propofol 32%). The results of the study indicate that both drugs are useful and controllable sedative agents for surgery under regional anaesthesia, provided that measures for continuous monitoring of respiration and emergency care are guaranteed.

Anesthesia, Epidural↗