Biomedical subjects

S Zielmann

Publications and source records attributed to S Zielmann.

30 records · Page 2Linked to original sources

PubMed1992

[Polytrauma following a fall from a great height. The injury pattern and the intensive medicine aspects].

We report on 10 polytraumatised patients who were treated in an ICU after a free-fall injury. The injury pattern of these patients proved to be relatively uniform. Brain oedema occurred in many victims. Remarkable was the fact that 8 out of 10 patients developed a pneumothorax, but only three of them had rib fractures on the same side. All patients suffered from fractures of the extremities with the lower extremities being affected more often. Abdominal injuries were not of importance.

Abdominal Injuries↗

PubMed1992

Hepatic disposition of methohexitone in patients undergoing coronary bypass surgery.

In order to clarify the relative contribution of hepatic metabolism to the short term disposition of methohexitone, we have measured hepatic blood flow during induction of anaesthesia with a 1.5-mg kg-1 i.v. bolus dose of methohexitone. Median hepatic clearance was 1.01 litre min-1 and hepatic extraction 87%. As a consequence of the high hepatic extraction, the hepatic clearance of methohexitone was closely dependent on hepatic plasma flow.

Adult↗

PubMed1992

[Is the lithium chloride-coated heat and moisture exchanger a danger for patients?].

Such hygroscopic compounds as LiCl, CaCl2, and MgCl2 are used to improve water retention capacity and, as a consequence, the effectiveness of heat and moisture exchangers (HME). Resorption of these substances via the bronchopulmonary tract and a resulting systemic action cannot be excluded, especially if additional active moisturizing devices are used. The narrow therapeutic range of lithium is known, as are its unwanted side effects, such as nausea, vomiting, somnolence and even cardiac arrhythmia. These are symptoms that also frequently occur during anaesthesia and intensive care, so that differentiation against effects of lithium is nearly impossible. We investigated whether, in theory and in practice, LiCl-coated HME could result in effective Li plasma concentrations. We measured (1) total LiCl content of HMEs, (2) release of this content, simulating the worst-case situation with a breathing model, and (3) lithium plasma concentrations of adult patients being ventilated during anaesthesia with a rebreathing circuit and LiCl-coated HME, but with no additional active moisturizing system incorporated. RESULTS. The results show striking differences with LiCl content ranging from 3 to 251 mg varying not only between different types of HME but also within the same lots. After 20 min of ventilation more than 90% of the LiCl coating was rinsed into the test lung of the breathing model. In practical use, we observed an increase in lithium plasma concentration in 3 of 20 investigated patients. The plasma values of maximum 49.5 micrograms/l (= 0.007 mmol/l) do not amount to potentially toxic concentrations. Nevertheless, clinically relevant concentrations might occur in patients with small distribution volumes, e.g. newborns or infants with frequent exposition within short intervals such as in intensive care units. The differences in lithium content also indicate qualitative differences in water retention capacity. Because of the potential side effects of lithium, we prefer qualitatively equivalent HMEs, e.g., with MgCl2 or CaCl2 as hygroscopic substance.

Adult↗

PubMed1992

[Effects of R80122. The influence of a new phosphodiesterase inhibitor on global and intestinal hemodynamics in coronary surgery patients].

Phosphodiesterase III inhibitors have been established in recent years in the therapy of congestive heart failure. Many disadvantages, such as extensive vasodilation and the lack of proven positive inotropic properties combined with thrombepenia and elevation of transaminases, have complicated the handling of the drug in clinical practice. Enoximone, an imidazole derivative, has been demonstrated to be more cardioselective and vasodilation has been found to be less pronounced than with amrinone. As a consequence, research was performed to enhance the cardioselectivity of phosphodiesterase III inhibitors by reduction of non-specific cross-reactivity with other phosphodiesterases, and R80122 (Janssen Pharmaceutics, Belgium) was introduced into clinical practice. R80122 ((E)-Ncyclohexal-N-methyl-2[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1b]-quinazolin-7-yl)methylene] amino] oxy] acetamide) is a selective inhibitor of phosphodiesterase (PDE) IIIc, which is localized in the myocardium. Thus, its inhibition leads to a positive inotropic effect, whereas phosphodiesterase IIIRo is found in the vessel wall and causes vasodilation. This study was performed to investigate the hemodynamic profile of R80122 under clinical conditions. Additionally, the intestinal hemodynamics were recorded and changes in intestinal perfusion compared with changes in global hemodynamics. METHODS. The study was thoroughly discussed and approved by the local ethics committee; all patients gave written informed consent. The investigation was performed on ten male patients who were about to undergo elective coronary artery bypass surgery. History, physical examination and laboratory results were within the normal limits and revealed no evidence of liver disease. The usual medication was continued until the day before the operation. Premedication consisted of 2 mg flunitrazepam p.o. in the evening before the operation and 1.5 h before induction of anaesthesia. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. After induction of anaesthesia (MP1), after application of a bolus dose of R80122 (0.3 mg/kg BW) (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Anaesthesia was induced with a bolus dose of 0.2 mg/kg BW etomidate, 7 micrograms/kgBW fentanyl and 0.1 mg/kgBW pancuronium and maintained with a continuous infusion of 20 micrograms/min fentanyl, 300 micrograms/min midazolam and mechanical ventilation with O2/N2O at an FiO2 of 0.5. Statistical analysis was performed using the Wilcoxon-Mann-Whitney U test comparing the results after induction of anesthesia (MPI) with those after application of R80122 (MPII) and the results of MPII with those at sternotomy (MPIII). Statistical significance was assumed at P less than 0.05. RESULTS. After the induction of anaesthesia, the median heart rate (HR) was 56/min and did not change after administration of R80122. During sternotomy there was a significant increase in the HR from 64 to 78/min (P less than 0.05). Median arterial blood pressure (MAP) tended to decreased from 91 mm Hg after induction of 77 mm Hg after administration of R80122, although there was no statistical significance because of interindividual differences in the tendencies. At sternotomy, MAP remained unchanged. Cardiac output (CO) increased by 60% after administration of R80122 (P less than 0.01) and did not change during sternotomy. As a consequence of the changes in HR and CO, stroke volume (SV) increased by 22% after administration of R80122 (P less than 0.025) and decreased to control values during sternotomy.

Adult↗

PubMed1992

[Endotracheal suctioning using a 24-hour continuous system. Can costs and waste products be reduced?].

Suctioning of the airways is often required in critically ill, intubated, or tracheotomised patients. In addition to the primary cost of these disposable materials, expenditures for waste disposal and environmental problems due to plastics should also be considered. In this study, the primary costs and amount of waste products of the closed suction system "Trach Care" were compared with a conventional disposable system. Other advantages and disadvantages of a closed suction system are discussed. METHODS. In this prospective, randomised investigation, both the open disposable suction system and the closed Trach Care system were used, in 60 patients (30 in each group) who were intubated for 1 week or more. During the first 7 days, we counted the number of times endotracheal suctioning was performed and measured the time it took. The costs of purchasing the systems, amounts of waste products, and costs of disposal were compared. RESULTS. The frequency of endotracheal suctioning was quite different from patient to patient and varied from 6 to 41 times per day. On average it was necessary 15 times per day per patient in both groups. Using the disposable system, a mean time of 3.5 min was measured in contrast to 2.5 min with the closed system. The costs of purchase were much lower with the disposable system taking into account all materials needed (17.36 DM vs 53.36 DM per day), whereas the weight of litter produced by the closed system was lower (429 g vs 745 g per day), the costs of disposal being accordingly different. During endotracheal suctioning O2 desaturation was not observed with the closed system, whereas in patients with acute respiratory failure O2 saturation fell rapidly from 90% to as far as 70% when a disposable system was used. CONCLUSION. The closed Trach Care suction system is more expensive to acquire, but may reduce the risk of exogenous nosocomial pneumonias as disconnections from the ventilator are minimised. The workload, weight of waste products, and costs of disposal are lower using the Trach Care system. From the physician's viewpoint, the main advantage of the Trach Care system becomes evident in patients with acute respiratory failure and patients with elevated intracranial pressure. In these cases, we now favor the Trach Care system as a matter of principle.

Anesthesiology↗

PubMed1992

Individualized dosage of gentamicin: a programmed pocket calculator is useful only when applied properly.

Various methods of gentamicin dosing were compared in order to evaluate factors that prevent achievement of therapeutic peak and trough plasma concentrations in every patient. When standard doses of 3 x 80 mg of gentamicin/day (i.e., 3 x 170 mumol/day) were administered, only 26% of peak and 51% of trough plasma concentrations were within the desired range. This percentage increased for peak levels to 54% (p less than 0.001) when physicians were instructed in the use of a programmed pocket calculator (PPC) and to 70% (p less than 0.001) when in addition the nursing staff was trained. The best results were achieved when dosing and blood sampling were supervised by a single trained person, 76% of initial peak and 71% of initial trough levels being within the therapeutic range. In this group of patients, further dosage adjustments by the PPC achieved 92% of peak levels in the desired range, while no patient had elevated trough levels. Analysis of the factors that led to these results revealed that neither the laboratory nor the PPC are limiting factors for optimal results. The goal of therapeutic plasma concentrations can be achieved, but requires appropriate attention to the accuracy of blood sampling and dosing. For this purpose, a special program, i.e., more than ordinary attention to drug therapy, is needed.

Adolescent↗

PubMed1992

[Hepatic elimination of thiopental in heart surgery patients].

Thiopental is a hypnotic drug that is widely used for the induction of anaesthesia. The mechanism of the short-term action is based on the rapid distribution of the drug, and in contrast to methohexital, the metabolism of thiopental is not relevant in use in conditions of operative anaesthesia. However, in neurotraumatology thiopental is frequently used as continuous infusion for several days to reduce cerebral metabolism. Under these circumstances, the elimination of thiopental becomes the most important factor for the duration of action. In order to clarify the relative contribution of the liver to the disposition of thiopental, hepatic blood flow was measured during the induction of anaesthesia and at sternotomy combined with the determination of plasma concentrations of the drug in arterial and hepatic venous blood, making it possible to calculate the hepatic and total plasma clearance of thiopental. METHOD. The study was thoroughly discussed and approved by the local ethics committee, and all patients gave informed written consent. The investigation was performed in 10 male patients (as detailed in Table 1), who had been referred for elective coronary artery bypass surgery. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. Before induction of anaesthesia (MP1), after induction (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Additionally, arterial and hepatic venous plasma concentrations of thiopental were determined by gas chromatography after induction until the extracorporeal circulation was started. Anaesthesia was induced with a bolus dose of thiopental 4 mg/kg body wt, fentanyl 7 micrograms/kg and pancuronium 0.1 mg/kg and maintained with a continuous infusion of fentanyl 20 micrograms/min and mechanical ventilation with O2/N2O at an FiO2 of 0.5. RESULTS. Median arterial pressure (MAP) decreased from 89 mmHg to 74 mmHg after induction and rose again to reach 104 mmHg at sternotomy. Cardiac output (HZV) also decreased from 6.17 l/min to 4.76 l/min after induction, but remained unchanged at sternotomy (Table 2). Hepatic plasma and blood flow showed no significant changes but tended to decrease after the induction of anaesthesia. Hepatic blood flow was constantly 26-28% of cardiac output. In the same way, intestinal oxygen consumption (VO2) did not change significantly, but the tendency was identical to that with hepatic perfusion. Hepatic clearance of thiopental as the product of hepatic extraction of thiopental (with a median value of 0.29) and hepatic plasma flow was 0.21 l/min. CONCLUSIONS. Thiopental is subject to a relatively low hepatic extraction of 0.29. Thus, changes in hepatic perfusion do not influence the elimination of thiopental. The actions of thiopental on global hemodynamics are comparable with the results found in the literature, characterized by a significant reduction in MAP and cardiac output after induction. The hepatic clearance of thiopental found in this study, with an absolute value of 0.21 l/min, is absolutely comparable with the data for total-body clearance reported in the literature. It is concluded that the liver is the only organ responsible for the elimination of thiopental in humans.

Adult↗

PubMed1985

Effects of isoprenaline and glucagon on insulin secretion from pancreatic islets.

The effects of isoprenaline and glucagon on insulin secretion from pancreatic islets were investigated. In the presence of high concentrations of isoprenaline (10-50 mumol/l), glucose-induced (20 mmol/l) insulin secretion from isolated perifused mouse islets was inhibited. This inhibition was apparently mediated by alpha 2-adrenoceptors, as it was antagonized by rauwolscine. At low concentrations isoprenaline (0.1 or 1 mumol/l) did not affect glucose-induced (2.5; 10 or 20 mmol/l) insulin secretion from perifused mouse or rat islets, even if alpha 2-adrenoceptors were blocked by rauwolscine. A stimulatory effect of isoprenaline on insulin secretion was also not observed in the perfused rat pancreas. However, when incubated mouse islets were exposed to glucose (10 mmol/l), insulin secretion was further enhanced by isoprenaline (0.5 mumol/l). To elucidate the underlying mechanism, the effects of glucagon on insulin secretion were investigated, because glucagon is released from the pancreatic A-cells during stimulation with isoprenaline and is accumulated in the islets and the surrounding medium during incubations of pancreatic islets. Indeed, glucagon stimulated insulin secretion from perifused mouse islets in the presence of high glucose (10 or 15 mmol/l) concentrations but not of low glucose (5 mmol/l) concentrations. Thus it is concluded that direct beta-adrenergic stimulation of pancreatic B-cells does not occur in mouse or rat pancreatic islets. Augmentation of glucose-induced insulin secretion by isoprenaline observed in incubation systems can be explained as a result of stimulation by glucagon, which is released from pancreatic A-cells by isoprenaline.

Animals↗

PubMed1985

The dihydropyridine derivative, Bay K 8644, enhances insulin secretion by isolated pancreatic islets.

The effects of the dihydropyridine derivative Bay K 8644 upon insulin secretion by perifused isolated mouse pancreatic islets were examined. At a non-stimulatory glucose concentration (5 mmol/l) Bay K 8644 (1 mumol/l) did not stimulate insulin release. However, the same drug concentration enhanced the insulin secretory responses to an intermediate (15 mmol/l) or high (30 mmol/l) glucose concentration by 80 or 90%, respectively. Bay K 8644 was half maximally effective at 0.1 mumol/l and maximally effective at 1 mumol/l. The results are compatible with the view that voltage-dependent calcium channels are essential for stimulus-secretion coupling in pancreatic B-cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1985

Secretory, enzymatic, and morphological characterization of rat pancreatic endocrine tumours induced by streptozotocin and nicotinamide.

Rat pancreatic endocrine tumours were induced by administration of streptozotocin plus nicotinamide. Fifteen to eighteen months later tumours with wet weights of 0.1 to 224 mg were isolated. These tumours were compared with normal rat pancreatic islets. Insulin release from perifused tumours was stimulated by D-glucose, L-leucine, 2-ketoisocaproate, and D-glyceraldehyde, potentiated by theophylline and inhibited by norepinephrine. Compared with isolated rat pancreatic islets, however, insulin secretory responsiveness to glucose stimulation and insulin content were reduced in tumour tissue. Hypoglycaemia in tumour bearing rats and impaired diffusion of insulin out of the tumours may explain this difference. The pattern of enzyme activities observed in tumour tissue was typical for pancreatic endocrine tissue. The activities of succinate dehydrogenase, the two types of the monoamine oxidase, and alpha-glucosidase were in the normal range in tumour tissue. Only the activities of 5'nucleotidase and glutamate dehydrogenase were decreased. Immunocytochemical analysis of the tumours revealed that they contained an average of 91% B-cells. In addition 8% of D-cells were encountered. Proportions of A-cells and PP-cells ranged below 1%. Thus this endocrine tumour of the pancreas with a high proportion of functionally intact B-cells is an interesting model for studying regulation of secretion and endocrine tumour development.

Adenoma, Islet Cell↗

PubMed1984

Regulation of insulin secretion by energy metabolism in pancreatic B-cell mitochondria. Studies with a non-metabolizable leucine analogue.

In mouse pancreatic islets the kinetics of insulin secretion and O2 uptake in response to the non-metabolizable leucine analogue (+/-)-BCH (2-endo- aminonorbornane -2-carboxylic acid) were compared. In addition, the fuel-mobilizing effect of (+/-)-BCH was studied with a mitochondrial fraction from islets. (1) Within 2 min 20 mM-(+/-)-BCH markedly enhanced insulin release or O2 consumption by islets respiring in the absence of exogenous fuels. During prolonged exposure to 20 mM-(+/-)-BCH secretion declined more rapidly than O2 uptake. (2) L-Glutamine (10 mM) prevented the decrease of both insulin release and O2 uptake of islets exposed to 20mM-(+/-)-BCH. During the second phase of insulin release in response to 20 mM-(+/-)-BCH + 10 mM-L-glutamine, kinetics of secretion and respiration correlated closely. (3) Initial peaks were consistently seen in the (+/-)-BCH-induced secretory profiles, but never in the respiratory profiles. (4) In contrast with L-glycerol 3-phosphate, L-malate or pyruvate, L-glutamine or L-glutamate maintained low rates of oxidative phosphorylation in B-cell mitochondria. The effects of L-glutamine or L-glutamate were potentiated severalfold by (+/-)-BCH. (5) The effects of other branched-chain amino acids on oxidative phosphorylation resembled their effects on insulin release, redox state of nicotinamide nucleotides and glutamate dehydrogenase activity. (6) The results support the view that (+/-)-BCH stimulates insulin secretion via a primary enhancement of hydrogen supply to the respiratory chain of B-cell mitochondria.

Adenosine Triphosphate↗

PubMed1983

Effects of alpha-adrenoceptor antagonists on clonidine-induced inhibition of insulin secretion by isolated pancreatic islets.

The effects of clonidine, yohimbine, corynanthine and prazosin on glucose-induced insulin secretion by incubated or perifused mouse pancreatic islets were investigated. Clonidine (0.1 microM) inhibited glucose-induced insulin secretion alone and in the presence of yohimbine (0.1 microM), corynanthine (10 microM) or prazosin (1 microM). In higher concentrations, yohimbine (1-10 microM) antagonized the inhibitory effect of clonidine (0.1 microM) upon glucose-induced insulin secretion by incubated islets and by perifused islets. The results support the view that adrenergic inhibition of insulin secretion is mediated by alpha 2-adrenoceptors on pancreatic beta-cells.

Adrenergic alpha-Antagonists↗