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Biomedical subjects

L Wiklund

Publications and source records attributed to L Wiklund.

At least 217 records · Page 12Linked to original sources

A study of the de- and regenerative changes in the sympathetic nervous system of the adult mouse after treatment with the antiserum to nerve growth factor.

In the adult mouse, the antiserum to nerve growth factor (NGF) induced marked atrophic changes of the ganglionic cell bodies in the superior cervical ganglion (SCG) and a disappearance of adrenergic nerve terminals in several peripheral tissues. By fluorescence histochemistry a lower-than-normal content of the noradrenaline (NA) transmitter was observed within the entire adrenergic neurone only 1 day after a single injection of NGF-antiserum (0.1 ml/g body weight). An atrophy of adrenergic nerve cell bodies and a disappearance of adrenergic nerve terminals were observed after 3 days, but the antiserum-induced effects did not appear maximally developed until 7 days after treatment. These fluorescence histochemical findings were paralleled by a gradual decrease of the endogenous NA levels in peripheral tissues and also of the weight of the SCG. A gradually proceeding restoration towards normal of the adrenergic innervation apparatus was observed fluorescence histochemically following a 5-day treatment with NGF-antiserum (0.1 ml/g body weight each dose), and after 6 weeks to 3 months a normal or close to normal fluorescence microscopical appearance was regained in the peripheral tissues and also in the SCG. These findings were parelleled by the results of the determinations of endogenous NA in peripheral tissues and by the results of weighing the SCG. We discuss some important differences between NGF-antiserum and 6-hydroxydopamine with respect to their mode of action on the mature sympathetic nervous system. Finally, we suggest that a decreased availability of NGF in a terminal area, due to an interference with endogenous NGF by NGF-antibodies, may temporarily result in an impaired function of the supplying adrenergic neurone, including a degeneration of nerve terminals.

Animals↗

Postoperative hepatic blood flow and its relation to systemic circulation and blood gases during splanchnic blockade and fentanyl analgesia.

Thirty-four patients with gallbladder disease, but otherwise healthy, were studied in connection with cholecystectomy. For postoperative analgesia, 22 patients were given a posterior splanchnic blockade with 0.5% plain lidocaine, and 12 were injected intramuscularly with fentanyl in a dose of 3.5 mug/kg b.w. Postoperatively, before administration of the analgesic agent, the cardiac output, mean arterial blood pressure, heart work and estimated hepatic blood flow were increased and the total peripheral resistance, splanchnic vascular resistance, arterial oxygen tension and base excess values were decreased. Fentanyl, in addition to its analgesic effect, also decreased the arterial oxygen tension and pH and increased the arterial carbon dioxide tension. There was little change in cardiac output, mean arterial blood pressure and estimated hepatic blood flow. Following splanchnic blockade, on the other hand, pain relief was accompanied by a decrease in cardiac output, mean arterial blood pressure and heart work to about the preoperative level, while the estimated hepatic blood flow remained unchanged and the splanchnic vascular resistance decreased rapidly. Neither total peripheral resistance nor blood gases altered as a result of splanchnic blockade.

Adult↗

Splanchnic oxygen uptake in relation to systemic oxygen uptake during postoperative splanchnic blockade and postoperative fentanyl analgesia.

In 34 patients with gallbladder disease, but otherwise healthy, the systemic and splanchnic oxygen uptake were studied in connection with cholecystectomy. Postoperatively, 22 patients were given a posterior splanchnic blockade with 0.5% plain lidocaine, and 12 were given fentanyl intramuscularly in a dose of 3.5 mug/kg b.w. Postoperatively, before the analgesic agent was administered, both the systemic and splanchnic oxygen uptake were increased by 40--50%, the splanchnic fraction of the systemic oxygen uptake being the same as preoperatively. Following administration of fentanyl, as well as after splanchnic blockade, the systemic oxygen uptake decreased almost to the preoperative level. The splanchnic oxygen uptake, however, did not change after fentanyl administration but increased further significantly following splanchnic blockade. The splanchnic fraction of the systemic oxygen uptake increased rapidly after the blockade, while it increased slowly after fentanyl administration.

Adult↗

Effects of abdominal surgery under general anaesthesia and of postoperative analgesic therapy on splanchnic exchange of some blood borne energy metabolites.

Sixteen patients with gallbladder disease, but otherwise healthy, were studied in connection with cholecystectomy. For postoperative analgesia, seven patients were given a posterior splanchnic blockade, 30 ml of 0.5% plain lidocaine, and nine patients were given fentanyl intramuscularly in a dose of 3.5 mug/kg b.w. Immediately after the operation and before analgesia, the arterial blood concentrations of glucose, lactate, glycerol, 3-hydroxybutyrate, and free fatty acids increased significantly. The splanchnic exchange of these metabolites was also significantly increased, except for glucose, the splanchnic release of which was significantly reduced. Induction of analgesia, both methods, was followed by a rapid significant decrease of the arterial blood concentration of glycerol, which tended to rise later when the analgesia disappeared. The arterial blood concentration of glucose and lactate showed a tendency to decrease slowly following both kinds of analgesia, while the arterial blood concentration of 3-hydroxybutyrate remained stable. The splanchnic release of glucose was significantly reduced after administration of fentanyl, while it increased significantly following splanchnic blockade, the splanchnic glucose release being correlated to arterial blood pH. The splanchnic release of 3-hydroxybutyrate was significantly reduced during maximal analgesia in both groups. The splanchnic uptakes of glycerol and free fatty acids were correlated to their splanchnic inflows.

Adult↗

Propantheline bromide in massive upper gastrointestinal haemorrhage.

The effectiveness of the anticholinergic, propantheline bromide, administered parenterally in patients with upper gastro-intestinal bleeding has been investigated in a double-blind study. The basic material consisted of 99 patients. No differences were found between the group receiving propantheline bromide and the group receiving placebo in regard to clinical factors such as duration of intensive care, total hospital stay and surgical frequency. However, 21 patients under 50 years of age showed a significantly lower blood transfusion requirement with the use of propantheline bromide.

Adult↗

Distribution and numbers of indoleamine cell bodies in the cat brainstem determined with Falck-Hillarp fluorescence histochemistry.

Using the Falck-Hillarp method, the cat brainstem was found to contain approximately 60,000 indoleamine (IA) cells. Most of these (46,000 or 77%) are located within the raphe nuclei. Nissl-stained material demonstrated both medium- and small-sized perikarya in the raphe nuclei, and quantitation revealed that the IA cells comprise only part of the medium-sized cells. Thus, the raphe dorsalis holds about 24,000 IA cells representing some 70% of its medium-sized cells. Corresponding values were for raphe pallidus 8,000 IA cells (55%), raphe centralis superior 7,400 (35%), raphe magnus 2,400 (15%), raphe obscurus 2,300 (33%), linearis intermedius 2,100 (23%), and raphe pontis 280 (9%). A considerable number of IA cells (13,600, representing 23% of the total) were found in locations outside the raphe nuclei: in ventral brainstem as lateral extensions from the raphe, among the bundles of fasciculus longitudinalis medialis, in periventricular gray and adjacent tegmentum, mixing with the noradrenergic cells of the locus coeruleus complex, among the mesencephalic dopamine cells, and in the nucleus interpeduncularis.

Animals↗

Effects of waste incineration combustion emissions measured by some toxicity test systems.

The toxicity of combustion emissions from a municipal incineration plant was tested in a series of rapid test methods. The series included tests concerning cellular energy metabolism, cellular detoxification and mutagenicity. In the most sensitive test systems, brown adipocytes and mitochondria, an effect was observed at an emission extract concentration corresponding to 0.02 m3 of exhaust. The results indicate an influence on the mitochondrial level as well as the premitochondrial level. In Ames' test concentrations corresponding to up to 0.3 m3 exhaust did not increase the number of revertants, although the chemical analysis of the emission indicates that the combustion emission contains mutagenic substances.

Adipose Tissue, Brown↗

Sopiens suscitans.

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Anesthesia, Inhalation↗

Pharmacokinetics and effects of 9-amino-1,2,3,4-tetrahydroacridine in the immediate postoperative period in neurosurgical patients.

STUDY OBJECTIVE: To determine the effects of intravenous (IV) 9-amino-1,2,3,4-tetrahydroacridine (THA) on postoperative somnolence in comparison to its pharmacokinetics. DESIGN: Open-label study of the pharmacokinetics and effects of THA. SETTING: Postoperative intensive care ward at the Department of Neurosurgery, Uppsala University Hospital, Sweden. PATIENTS: Ten neurosurgical patients immediately after their operations were given 30 mg of THA for reversal of postoperative somnolence. INTERVENTIONS: Plasma concentrations of THA and, in seven cases, the metabolite 1-hydroxy-THA were assayed using high-performance liquid chromatography. The pharmacokinetic data were compared to the degree of sedation and pain relief. After an IV dose of 30 mg THA, plasma concentrations were fit to an open two- or three-compartment model. MEASUREMENTS AND MAIN RESULTS: The antagonistic effect of THA on sedation occurred immediately following IV administration and lasted 60 to 90 minutes. At a mean plasma THA concentration of 44 +/- 18 ng/ml, patients were resedated. There was no obvious relation between analgesia and plasma THA concentrations. Side effects such as nausea, salivation, and lower heart rate (HR) were observed in several patients. Plasma clearance (C1) was high and showed a twofold inter-individual variation, with a mean of 2.64 +/- 1.17 L/h. Volume of distribution (Vd gamma) varied between 300 and 850 liters, with a mean of 477 +/- 185 liters. The plasma half-lives of rapid and slow distribution, and elimination were 2.1 +/- 0.7 minutes, 26 +/- 18 minutes, and 133 +/- 48 minutes, respectively. Maximum plasma concentrations of 1-hydroxy-THA were 27 to 90 ng/ml in five patients; the concentration was below 1 ng/ml in two other patients. CONCLUSIONS: The duration of the effects of THA as an antagonist of postoperative sedation was only about double that seen previously after the IV administration of physostigmine in a similar group of patients, although the elimination half-life of THA was six times longer than that of physostigmine. A larger dose of THA possibly could have been given to prolong the period of antagonism of sedation, but the profile of adverse effects seen even at the doses used precluded that option.

Adult↗

Postanesthesia monitoring revisited: frequency of true and false alarms from different monitoring devices.

STUDY OBJECTIVES: To determine the frequency of true and false alarms and to determine the frequency of alarm failures for various parameters when using a postanesthesia monitoring system. DESIGN: Open prospective study. SETTING: Postanesthesia care unit at a university hospital. PATIENTS: 123 ASA physical status I-IV patients who underwent general or spinal-epidural anesthesia for general, urologic, orthopedic, ophthalmologic, otolaryngologic, or plastic surgery. MEASUREMENTS AND MAIN RESULTS: Monitoring included ECG, oxygen saturation, and respiratory rate (RR) by either transthoracic impedance or nasal-oral air-flow detection. We undertook careful, continuous observation of patients and monitors, recording of true and false alarms; the latter were defined as those coinciding with a clearly observed, unrelated cause. During a mean observation period of 101 minutes per patient, the average frequency of pulse oximetry alarms was once every 8 minutes, with 77% of the alarms being false, caused by sensor displacement, motion artifacts, poor perfusion, or a combination of these factors. Apnea alarms occurred on average once every 37 minutes, with the "false" fraction being 28% and 27% for impedance and flow detection, respectively. The impedance sensor failed to detect apnea on at least 6 occasions; the flow sensor failed on 1 occasion. The coincidence of pulse oximetry and apnea alarms was small, and ECG exhibited a low alarm rate but a high fraction of false alarms. Patients receiving opioids and neuromuscular relaxants had a higher frequency of "true" apneas than patients not receiving these drugs. No clear correlation was found in regard to age distribution, type of surgery, duration of anesthesia, oxygen administration, or ASA physical status between the patient groups that exhibited many apneas or many pulse oximeter alarms and the whole study population. CONCLUSIONS: The high frequency of apnea strongly motivates the use of continuous RR monitoring, preferably by flow-sensing techniques, since both central and obstructive apneas are then detected. Further study and development is necessary before pulse oximetry can be unconditionally recommended for postanesthesia monitoring.

Adolescent↗

Experimental model of cardiovascular post-resuscitation syndrome--no effect of platelet activating factor antagonism.

The cardiovascular instability seen in the reperfusion phase after resuscitation from cardiac arrest may contribute to secondary brain injury. The aim of the present study was to characterise post-resuscitation cardiovascular instability in an experimental model of cardiac arrest and to test if cardiovascular stability could be improved by pre-treatment with the platelet activating factor (PAF) antagonist BN52021. Ten anaesthetised pigs received pre-treatment with BN52021 before induction of ventricular fibrillation (arrest/BN52021 group), while ten animals received only the vehicle (arrest/vehicle group). After a non-intervention interval of 9 min, resuscitation was attempted. Resuscitated animals were observed for 5 h and compared to a sham arrest group of seven animals. The haemodynamic situation after resuscitation was characterised by a low cardiac output that was inadequate in relation to the oxygen demand, as reflected by a low mixed venous oxygen saturation. The arterial blood pressure was to some extent reduced and the filling pressures in both the right and left heart were increased, but urinary output was not reduced. The severe haemodynamic compromise was not adequately reflected by standard monitoring variables such as arterial blood pressure and urinary output. Pre-treatment with BN52021 was unable to improve any aspect of short-term survival or haemodynamic stability.

Acid-Base Equilibrium↗

Improved haemodynamics and restoration of spontaneous circulation with constant aortic occlusion during experimental cardiopulmonary resuscitation.

Continuous balloon occlusion of the descending aorta is an experimental method that may improve blood flow to the myocardium and the brain during cardiopulmonary resuscitation (CPR). The aim of the present investigation was to evaluate the effects of this intervention on haemodynamics and the frequency of restoration of spontaneous circulation. Ventricular fibrillation was induced in 39 anaesthetised piglets, followed by an 8-min non-intervention interval. In a haemodynamic study (n = 10), closed chest CPR was performed for 7 min before the intra-aortic balloon was inflated. This intervention increased mean arterial blood pressure by 20%, reduced cardiac output by 33%, increased coronary artery blood flow by 86%, and increased common carotid artery blood flow by 62%. All these changes were statistically significant. Administration of epinephrine further increased mean arterial blood pressure and coronary artery blood flow, while cardiac output and common carotid artery blood flow decreased. In a study of short-term survival, nine out of 13 animals (69%) in the balloon group and in three out of 13 animals (23%) in the control group had spontaneous circulation restored. The difference between these two proportions was 0.46, which was statistically significant with a 95% confidence interval from 0.12 to 0.80. In conclusion, balloon occlusion of the descending aorta increased coronary and common carotid artery blood flow and the frequency of restoration of spontaneous circulation. It was also noted that epinephrine appears to augment the redistribution of blood flow caused by the aortic occlusion.

Adrenergic Agonists↗

Cap and polyA tail enhance translation initiation at the hepatitis C virus internal ribosome entry site by a discontinuous scanning, or shunting, mechanism.

OBJECTIVES: Hepatitis C virus (HCV) does not replicate in vitro, suggesting that cultured cells may lack factors that are essential for efficient use of HCV messenger RNAs (mRNAs). Here, we have studied the efficiency of HCV mRNA translation compared with translation of capped and polyadenylated mRNAs in human cells. STUDY DESIGN/METHODS: We have generated noninfectious minivirus mRNAs from an infectious HCV genome. These mRNAs were transfected into human cells, and the translation efficiency was determined. RESULTS: Hepatitis C virus mRNAs under control of the HCV internal ribosome entry site (IRES) were inefficiently translated compared with capped and polyadenylated mRNAs. Addition of a cap and a polyA tail on the HCV mRNAs revealed that these structures interacted with the hepatitis C IRES in a synergistic manner to load ribosomes onto the HCV mRNAs, thereby strongly enhancing translation. The positive effect of the cap and the polyA tail on initiation of translation at the initiator AUG embedded in the HCV IRES was the result of a discontinuous scanning, or shunting, mechanism. CONCLUSIONS: The results demonstrated that recruitment of ribosomes to the HCV mRNAs was inefficient in dividing cultured cells. Factors that are necessary for efficient translation of the HCV mRNAs in hepatocytes may be absent or inactive in cultured cells. This may be one reason for the inefficient replication of the HCV in vitro.

5' Untranslated Regions↗