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Biomedical subjects

R Scherer

Publications and source records attributed to R Scherer.

At least 55 records · Page 3Linked to original sources

[The effect of substitution with AT III- and PPSB-concentrates in patients with terminal liver insufficiency].

UNLABELLED: Patients with end-stage liver disease frequently develop combined coagulopathies due to increased procoagulant and fibrinolytic turnover as well as thrombocytopenia. The onset of clinical symptoms of a haemorrhagic diathesis requires balanced substitution of coagulation factors, since fresh frozen plasma alone does not always maintain a sufficient haemostatic potential in these patients. This substitution commonly follows standard rules based on the assumption that 0.5-1 IU of a coagulation factor or inhibitor concentrate given per kg body weight will increase its endogenous activity by 1%. We set out to investigate the validity of this standard regime in patients with end-stage liver disease scheduled for orthotopic liver transplantation. PATIENTS AND METHODS: Fifty-one adult patients were prospectively studied. In 37 patients with antithrombin III (AT III) activity < 70%, an AT III preparation (Kybernin, Behring, Marburg, Germany) was given preoperatively (mean dose 2616 +/- 207 IU) following standard calculations in order to increase endogenous activity to 80%. Twenty-seven of the patients had chronic hepatic failure (CHF group) with histologically proven cirrhosis and 10 had acute hepatic failure (AHF group). Blood samples were drawn prior to a 15-min infusion of AT III concentrate and 30 min thereafter. In 14 patients with prothrombin time (PT) < 40%, AT III levels had been corrected earlier during the clinical course to achieve activities > 70%. Prothrombin complex (PPSB, Beriplex, Behring, Marburg, Germany) was substituted (mean dose 2304 +/- 289 IU) to increase procoagulant activity to PT > 60%. Blood samples were drawn in the same fashion as in the AT III group. The amounts of AT III and PPSB concentrates (delta AT III, [IU/kg]; delta PPSB [IU/kg]) required to increase AT III activity and PT, respectively, by 1% were calculated. RESULTS: Standard calculations for AT III substitution indicated AT III recovery in all 37 patients who received AT III concentrate. However, there was a statistically significant difference between patients with CLF and ALF. In patients with CLF, delta AT III was found to be 0.8 IU/kg (+/- 0.1 SEM) and in those with ALF it was 1.5 IU/kg (+/- 0.1 SEM) (P < 0.05, t-test). In patients treated with PPSB concentrate, delta PPSB was 1.6 U/kg (+/- 0.2 SEM) for both CLF and ALF groups. CONCLUSIONS: In patients with end-stage liver disease standard rules for substitution with AT III-concentrate are adequate only for patients with CLF. In patients with ALF higher AT III doses are required to achieve the expected effect on endogenous AT III activity. Procoagulant activity, as reflected by PT, can be increased by 1% when 1.6 IU/kg PPSB concentrate is given. However, this study shows the effects of coagulation concentrates only 30 min after administration. An increased volume of distribution and increased turnover may explain the poor recovery of AT III activity in the ALF group, indicating that the dose of coagulation concentrate should be estimated against the background of the patient's clinical symptoms and diagnosis.

Adult↗

[Diagnosis and therapy of disseminated intravascular coagulation].

Consumptive coagulation disorders are frequently observed in critically ill patients secondary to other underlying diseases. Initial hypercoagulability leads to subsequent hypocoagulability due to consumption of procoagulant proteins, inhibitors, and platelets. This process evolves in three distinct phases: an initial increase in coagulation activity is characterised by the activation of coagulation factors and platelets without any clinical symptoms of a haemorrhagic diathesis. The ongoing process of activation and accelerated consumption of coagulation factors and inhibitors causes a critical reduction in the haemostatic potential. The time of onset of the clinical symptoms of bleeding depends on the patient's underlying disease and its pharmacological management. Coagulation processes that are restricted locally under normal conditions become disseminated when the inhibitory potential--mainly represented by antithrombin III (AT III)--is exhausted. Therefore, thrombin formation occurs, especially in the microcirculation, where fibrin clot deposition begins to cause inhomogeneities of blood flow and thus to reduce oxygen delivery to the tissues. Hypocoagulability, reactive hyperfibrinolysis, and diffuse bleeding lead to an irreversible systemic breakdown of haemostatic mechanisms (disseminated intravascular coagulation, DIC). The laboratory diagnosis of accelerated consumption is based on the course of global coagulation tests (e.g., prothrombin time, activated partial thromboplastin time, platelet count) and more sensitive ("dynamic") activation parameters such as prothrombin fragment F1 + 2, thrombin-AT III complex, fibrin monomers, or d-dimer. Measurements of plasminogen, tissue plasminogen activator, plasminogen activator inhibitor 1, and alpha 2-antiplasmin-plasmin complex provide information on fibrinolytic turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care↗

A new method of veno-venous bypass during human orthotopic liver transplantation.

Veno-venous bypass is commonly used during orthotopic liver transplantation, but there is some controversy as to whether it contributes to a better outcome. Low shunt flows frequently reduce the efficacy of portofemoro-axillary systems and so a percutaneous cannulation technique for the subclavian and femoral vein with large bore catheters was developed in order to facilitate bypass management. This study reports the performance and complications of a portofemoro-subclavian bypass system during the anhepatic phase of human orthotopic liver transplantation in 85 patients. A percutaneous cannulation technique and two 7 mm (subclavian and femoral) catheters, inserted pre-operatively, were used in a pump driven portofemoro-subclavian bypass system. Coagulation profiles, shunt flows, haemodynamic parameters, and peri-operative complications associated with bypass were recorded for each patient. Percutaneous cannulation of the left femoral and subclavian vein was successful in 78 patients (91.8%). Mean femoro-subclavian shunt flow was 1.45 l.min-1 (SD 0.37), and mean portofemoro-subclavian flow was 4.28 l.min-1 (SD 1.03). Although oxygen delivery was not maintained at pre-shunt levels (559.7 (SD 147) vs 506 (SD 107) ml.min-1.m-2, p < 0.05) renal perfusion pressure stayed above 50 mmHg (during shunt it was 56 (SD 9) mmHg). One intra-operative air embolism was observed (1.2%), and in one patient a myocardial infarction occurred during the anhepatic phase; neither complication was considered to be related to the percutaneous cannulation technique. There were no bleeding complications. After operation, all chest X rays were normal and clinical examination revealed no adverse effects of portofemoro-subclavian bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of hypertonic saline hydroxyethyl starch solution on collagen-induced platelet aggregation and ATP secretion.

OBJECTIVE: The purpose of this study was to investigate the effect of hypertonic (NaCl 7.5%) hydroxyethyl starch (HES 6%, molecular weight 200,000) (HHES) as used for small-volume resuscitation on global coagulation parameters and platelet function. DESIGN: Randomized, controlled clinical trial. SETTING: Intraoperative volume loading after induction of general anesthesia. PATIENTS: 27 consecutive patients [mean age 59 (22-76) years, mean body weight 69.8 (46-98) kg] undergoing abdominal surgery were studied. INTERVENTIONS: Global coagulation tests (aPTT: activated partial thromboplastin time; PT: prothrombin time; platelet count; thrombelastography: TEG), platelet aggregation and ATP release were measured before and 10 min after the application of 4 ml.kg-1 of HHES (study group H, n = 14) or HES (control group C, n = 13). RESULTS: The aPTT was prolonged and platelet count was significantly reduced in both study groups. In contrast to the HES group, clot formation time in the TEG was significantly prolonged and the maximum amplitude was reduced in the HHES group. Furthermore, platelet aggregation was significantly slowed down, whereas ATP release significantly increased in the HHES group. CONCLUSION: The changes in global coagulation parameters can be explained by dilutional effects of the infused solution. The hyperosmolar saline compound of the HHES solution obviously contributes to the slowing down of platelet aggregation. Osmotic stress and membrane pleating may aggravate HES-induced changes in membrane fluidity and microviscosity and thus explain this impaired interaction. The increase in ATP release suggests a change in receptor-second messenger interaction for delta granule release.

Abdomen↗

[Liver complications of HELLP syndrome--an indication for emergency liver transplantation?].

Three patients were treated suffering from a severe HELLP-syndrome. The problems as far as the diagnostic and therapy are concerned are discussed. All three patients had to be operated on in an emergency state. The operations were performed due to acute and severe abdominal bleeding. Two of the patients needed liver transplantation as an emergency procedure, one of them died after hepatectomy waiting for a graft. Another one died seven weeks after successful transplantation due to prolonged sepsis. The third patient is more than one year after transplantation alive and doing well.

Adult↗

[Liver complications in HELLP syndrome].

In a 5 years period 5 female patients suffering from a severe HELLP syndrome were treated. The problems concerning diagnostic and treatment are discussed. 3 patients had to be operated on in an emergency state. The operations were performed because of acute and severe abdominal bleeding. Two of the patients needed liver transplantation as an emergency procedure, one of them died after hepatectomy on the list. Another one died 7 weeks after successful transplantation in a state of prolonged sepsis. The two conservatively treated and the one transplanted patient are still alive and well.

Adult↗

[Normal findings with duplex sonography of liver blood vessels--experience in the examination of 100 patients with healthy livers].

100 patients of our kidney transplantation program and uneventful as regards their liver history were indexed by the pulsatile flow (PFI) of the hepatic artery and the damp curve (DI) of the hepatic veins. The average age of the patients was 36 years (20-50y). The pulsatile flow index (PFI) was calculated as 0.4 to 0.7. The damp index (DI) as 0.3 to 0.54. In 10 of these volunteers the measurement was performed 3 times per day for 5 days: there was no difference to be found in comparison to the values of the total group. The presented values of the PFI and DI give the normal range and will be the basis for further investigations in patients after liver transplantation or suffering from liver diseases.

Adult↗

[Measuring impedance for evaluating ischemia damage to the human liver in preparation for transplantation].

In 22 human donor livers the measurement of the non-invasive bioelectrical impedance was performed prospectively to evaluate the degree of tissue damage sustained during cold ischemia. The results of the measurement were correlated with liver function, the method of organ preservation and the period of ischemia. The impedance was measured in vivo as 620 ohm (at 192 Hz), the phase angle as -7.4 degrees (at 5 kHz). The results were compared with the data obtained from 72 patients who underwent elective laparotomies. The 22 donor livers were studied further during ischemia. The method was found to be a reliable way of detecting severe damage to the hepatocytes during the cold ischemia.

Adolescent↗

Acute liver necrosis in the HELLP syndrome: successful outcome after orthotopic liver transplantation. A case report.

We discuss the case of a 30-year-old primipara woman who developed a liver rupture as a complication of the HELLP syndrome. A liver necrosis and bleeding made a hepatectomy necessary. A portocaval shunt was able to maintain the patient until she underwent urgent liver transplantation. In an excellent state of recovery, the woman and her baby were discharged from the hospital 66 days after having been admitted.

Adult↗

Phonatory control in male singing: a study of the effects of subglottal pressure, fundamental frequency, and mode of phonation on the voice source.

This article describes experiments carried out in order to gain a deeper understanding of the mechanisms underlying variation of vocal loudness in singers. Ten singers, two of whom are famous professional opera tenor soloists, phonated at different pitches and different loudnesses. Their voice source characteristics were analyzed by inverse filtering the oral airflow signal. It was found that the main physiological variable underlying loudness variation is subglottal pressure (Ps). The voice source property determining most of the loudness variation is the amplitude of the negative peak of the differentiated flow signal, as predicted by previous research. Increases in this amplitude are achieved by (a) increasing the pulse amplitude of the flow waveform; (b) moving the moment of vocal fold contact earlier in time, closer to the center of the pulse; and (c) skewing the pulses. The last mentioned alternative seems dependent on both Ps and the ratio between the fundamental frequency and the first formant. On the average, the singers doubled Ps when they increased fundamental frequency by one octave, and a doubling of the excess Ps over threshold caused the sound pressure level (SPL) to increase by 8-9 dB for neutral phonation, less if mode of phonation was changed to pressed. A shift of mode of phonation from flow over neutral to pressed was associated with a reduction of the peak glottal permittance i.e., the ratio between peak transglottal airflow to Ps. Flow phonation had the most favorable relationship between Ps and SPL.

Air Pressure↗

Complications related to thoracic epidural analgesia: a prospective study in 1071 surgical patients.

In a prospective study, the complications of 1071 patients scheduled for thoracic epidural catheterization for postoperative analgesia (TEA) were studied. All catheters were inserted preoperatively between segment Th 2/3 and Th 11/12 under local anesthesia. Balanced anesthesia with endotracheal intubation and TEA were combined. Postoperatively 389 patients (36.9%) were monitored on a normal surgical ward. Buprenorphine, 0.15 to 0.3 mg, and if needed bupivacaine 0.375% 3-5 ml h-1 were given epidurally. Primary perforation of the dura occurred in 13 patients (1.23%). Radicular pain syndromes were observed in six patients (0.56%). In one patient (0.09%) respiratory depression was seen in close connection with the epidural administration of 0.3 mg buprenorphine. Although 116 patients (10.83%) showed one abnormal clotting parameter but no clinical signs of hemorrhage, there was no complication related to this group. No persisting neurological sequelae caused by the thoracic epidural catheters were found. In conclusion, continuous TEA with buprenorphine for postoperative pain relief after major abdominal surgery is a safe method without too high a risk of catheter-related or drug-induced complications, even on a normal surgical ward and when one clotting parameter is abnormal.

Adolescent↗

[Effect of dopexamine on the hemodynamics of coronary surgery patients with and without bisoprolol blockade].

Patients with coronary artery disease undergoing coronary artery bypass grafting can develop perioperative low cardiac output failure requiring positive inotropic support. Commonly, the sympathetic amines, dopamine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experience problems with such a treatment. Dopexamine, a new synthetic amine, possesses positive inotropic effects by indirect stimulation of the beta 1-receptors and direct stimulation of the beta 2-receptors. We therefore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade. In 12 patients with coronary artery disease classed as NYHA II or III, six without any beta-blocker medication, and six with beta 1-blocker medication (bisoprolol 5 mg), anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. Following intubation anesthesia was continued with 0.025 mg/kg/h fentanyl. In anesthesia steady state the patients of both groups were treated with 2 micrograms/kg/min dopexamine over a period of 15 min and then with 4 micrograms/kg/min dopexamine over a further period of 15 min. Measurements of cardiovascular dynamics included heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial blood pressure (MAP), coronary perfusion pressure (CPP), systemic vascular resistance (SVR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), pressure work index (PWI) and arterial-mixed venous oxygen content difference (AVDO2), which were monitored or calculated by standard formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

[Increasing the adhesion of glass ionomer cements in bracket bonding].

For attaching orthodontic brackets glass ionomer cements are being discussed as an alternative material to synthetic glues since they are less aggressive toward the tooth enamel. A serious disadvantage consists in a lower degree of adhesion to enamel. The adhesion can, however, be increased to some extent by enamel preparation. In order to investigate further improvement in this area, 250 freshly extracted bovine teeth were treated with 22 chemicals and their enamel-conditioning properties were tested. For the attachment of the brackets the glass ionomer cements AqaCem and Ketac-cem are used. Tensile shear tests were carried out with a Wolpert universal testing machine. Best results were obtained with the aromatic carbonacids benzoic acid and salicylic acid in acetonic solution. The mean adhesive power was 9.8 MPa. This means an increase of 38% as compared to other pre-conditioning materials such as polyacrylic acid. It can be assumed, that aromatic carbonacids as small, very reactive molecules can establish a closer contact to the phosphate groups of enamel than can the macromolecular polyacrylic acid. Thus, a further step on the way to using glass ionomer cements as a bracket bonding material seems to have been taken.

Adhesiveness↗

Partially hepatectomized rats: a model for the study of the effect of toxins on the plasma protein profiles of nascent hepatocytes.

A useful framework is proposed for unifying the synthesis of plasma proteins and their degradation by, or release from, liver cells of intact and partially hepatectomized rats, in which synthesis and release of acute-phase plasma proteins occur in synchrony with the internalization and catabolism of plasma and extracellular proteins. The catabolism of proteins and other hepato-intracellular glycoproteins during sepsis or trauma is essential to provide constituent amino acids and carbohydrates for the synthesis of acute-phase plasma proteins. Increases in the plasma levels of acute-phase response proteins in sham-operated rats reached a maximum between 1 and 2 d after mock surgery, and had returned virtually to control levels within 6 d. By contrast, acute-phase proteins in the plasma of partially hepatectomized rats were decreased by 10-20% of their initial values after 24 h. A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively. This delayed response suggests that the nascent liver cells had inherited the capacity of the parent cells to respond to inflammatory signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame for the application of toxin to nascent hepatocytes is suggested. An increased activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver tissue 19 h post partial hepatectomy suggested that hepatic regenerating factor(s) were produced in liver tissue via the hepatic bound and/or free neuraminidase-mediated desialylation of humoral substrates. By contrast, circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D-glucosaminidase were increased marginally after 24 h but had returned nearly to control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute-phase plasma proteins.

Acute-Phase Proteins↗