Central and renal hemodynamics, renal oxygenation, renal uptake of glucose, lactate, fats, renal carnitine metabolism, arterial atrial natriuretic factor (ANF) and catecholamine release were studied in sixteen adult beagle dogs during pentobarbital anesthesia. Renal cortical oxygen tension was recorded by means of a Silastic tonometer. Twelve animals underwent acute circulatory shock induced by intravenous Escherichia coli endotoxin 0.5 mg/kg. Four control dogs received normal saline. The endotoxin infusion resulted in decreased cardiac function, renal blood flow and renal cortical PO2. The renal venous PO2 increased during the experiment.Arterial and renal venous glucose concentrations increased transiently during endotoxemia. Circulating lactate concentrations increased significantly whereas the arteriovenous lactate difference remained almost unchanged. Renal uptake of lactate and glucose were not influenced during the moderate renal hypoperfusion caused by endotoxin.Arterial free fatty acid (FFA) concentrations increased significantly 2 hours after onset of the endotoxin infusion whereas renal venous FFA levels remained rather stationary. The renal uptake of FFA increased with increasing arterial FFA concentrations.Circulating free carnitine concentrations increased significantly in endotoxin shock. Blood acyl-carnitine concentrations remained essentially unchanged. Carnitine concentrations declined significantly in endotoxic renal tissue.The arterial concentrations of ANF, epinephrine, norepinephrine and the norepinephrine metabolite 3,4-dihydroxyphenylglycol (DHPG) increased in plasma during early endotoxemia. The levels of these hormones remained very low and constant in the controls.To summarize, endotoxin injection resulted in impaired renal perfusion and oxygenation, increased uptake of free fatty acids and unchanged uptake of glucose, lactate, glycerol and triglycerides. Decreased renal carnitine concentrations were observed. Arterial plasma concentrations of ANF and catecholamines increased in endotoxin shock.
Interest in low molecular weight heparins as potential antithrombotic agents has been stimulated by two observations. These were that low molecular weight heparins have a different anticoagulant profile from unfractionated heparin and that some low molecular weight heparins are less haemorrhagic in animal models than unfractionated heparins for equivalent antithrombotic effects. Subsequently, it was shown that low molecular weight heparins inhibit platelet function and impair vascular permeability less than unfractionated heparin and that low molecular weight heparins have a longer biological half-life than unfractionated heparin. A number of low molecular weight heparins have been evaluated in clinical trials in general surgery, orthopaedic surgery and in the treatment of venous thrombosis. Low molecular weight heparins are highly effective in orthopaedic surgery where they appear to be more effective than unfractionated heparin. Low molecular weight heparins have also been shown to be either as effective or more effective than unfractionated heparin in preventing post-operative thrombosis following general surgery. In preliminary studies, low molecular weight heparins appear to be as effective as unfractionated heparin in the treatment of venous thrombosis but larger studies are required using clinically relevant outcome measures.
Patients having major orthopaedic surgical procedures have a high risk of venous thromboembolism. The distribution of thrombi following hip surgery differs from most other high risk situations, as 30-40% of all thrombi occur in proximal veins and many are unassociated with distal vein thrombosis. Many of these thrombi are undetected by currently available screening tests, but are detected by venography. Of the various prophylactic methods available, oral anticoagulants, adjusted-dose heparin and low molecular weight heparins are most effective in hip surgery, and oral anticoagulants and external pneumatic compression are most effective in knee surgery.
Diet-induced thermogenesis (DIT) denotes the increase in energy expenditure that occurs in response to food ingestion. The purpose of the present study was to examine the possible influence of age, training state and sympatho-adrenal activity on the early phase of DIT in healthy individuals and further to study whether the magnitude of DIT is reduced in human obesity and, if so, to what extent DIT is influenced by weight reduction induced by surgical treatment, i.e. gastric banding or vertical banded gastroplasty. In addition, the effect of an artificial abdominal insulation on the DIT reaction was examined in healthy subjects in order to find out if the spontaneously enhanced thermal insulation of the body in obese individuals may be accompanied by a reduced DIT. The subjects were studied in the basal state and during 2-3 hours after a mixed meal. The energy expenditure was determined by indirect calorimetry. Blood temperature and blood flow in the hepatic vein were measured and splanchnic oxygen uptake and blood-drained heat from the splanchnic region were calculated. The meal was in liquid form, consisting of 17% kJ protein, 28% kJ lipids and 55% kJ carbohydrates, corresponding to either 60% of the individually measured 24-h resting energy expenditure or to 40% of the individually predicted basal metabolic rate. DIT was expressed as the average increase in energy expenditure above the basal level (means +/- SEM). After a 60% meal it was less (21 +/- 3%, P less than 0.01) in 8 elderly (70 +/- 1 years) and 7 middle-aged (51 +/- 3 yrs) individuals (24 +/- 2%, P less than 0.05) than in 10 young (27 +/- 1 yrs) men (29 +/- 2%). Its magnitude was similar (n.s.) in 7 well-trained men with a higher (58 +/- 2 ml/min/kg BW) maximal oxygen uptake (25 +/- 2%) and 7 sedentary individuals with a lower (39 +/- 2 ml/min/kg BW) aerobic capacity (29 +/- 2%). An intravenous pharmacological inhibition of the beta-adrenergic receptor function failed to influence the DIT in 10 men, irrespective of whether the beta-blockade was instituted by a selective-beta-1 antagonist (atenolol) or a non-selective blocker (propranolol). The DIT was 29 +/- 1% with and 29 +/- 2% (n.s.) without a beta-blockade and it was 29% in 2 subjects after 1 week of oral propranolol medication.(ABSTRACT TRUNCATED AT 400 WORDS)
After a short introduction (chapter 1), anatomy is described in chapter 2. The sphincter of Oddi (SO) can be divided into the choledochal, pancreatic and ampullar sphincter in addition to the intermediate fibres. In anatomic studies the pancreatic and ampullar sphincters are described in only one third and sixth respectively. This is in disaccordance with manometric studies where SO activity always is registered in the pancreatic sphincter after total biliary sphincterotomy. Chapter 3 discusses whether or not the SO is a true sphincter. Activity simultaneous with the duodenum occurs in the interdigestive phase III, but more often duodenal and SO activity is dissociated. It is concluded that the vast evidence supports the SO as a true sphincter. Chapter 4 concerns methods for investigation of the SO activity. The manometric methods are divided into direct and indirect studies, and advantages and disadvantages are discussed. The direct manometric method employing a perfusion system is highlighted, and interpretation of tracings and artifacts described. In chapter 5 physiological aspects are considered. Slow waves are present in the SO, and the activity related to the migrating motor complexes of the duodenum. Apart from interdigestive variation the food stimulated pattern is mentioned. Nervous and hormonal control as well as the relation to other parts within and outside the pancreatico-biliary system is outlined. The SO receives nervous fibres from both the sympathetic and the parasympathetic system. The alfa- and cholinergic neurons stimulate whereas the beta-neuron inhibits the SO. Furthermore inhibitory non-adrenergic, non-cholinergic neurons are present. Cholecystokinines inhibitory action on the SO are brought about via a stimulation of inhibitory neurones since the peptide has a direct stimulatory action on the SO muscle. The most important reflex regulation of the SO is elicited by gallbladder pressure increase with inhibition of the SO. Probably a similar reflex relationship exists between the common bile duct and the SO. The SO is considered important in the regulation of biliary flow, and probably also pancreatic flow, although the latter is only poorly studied. Furthermore the SO is believed to play a role in the prevention of reflux from the duodenum. In chapter 6 studies in normals, controls and patients with diseases in the biliary and pancreatic system are surveyed. In patients with gallbladder stones no changes in SO activity has been disclosed. In patients with common bile duct stones some have found increased antiperistalsis, others not.(ABSTRACT TRUNCATED AT 400 WORDS)
Pharmacokinetic parameters of low molecular weight heparins (LMWHs) are commonly determined by quantifying the biological activity. Such pharmacodynamic determinations should be extrapolated with care to provide pharmacokinetic information. Direct comparisons should only be drawn between LMWHs given at the same dose, determined by the same test. This is especially important since different tests estimate potency, bioavailability, and duration differently. There is a strong correlation between the ratio of anti-Xa:anti-IIa activities determined in vitro and mean residence time in vivo. Each LMWH has a characteristic pharmacokinetic and pharmacodynamic profile and cannot be considered bioequivalent either at doses recommended for prophylaxis or at anti-Xa adjusted doses. These conclusions emphasize that LMWHs are not interchangeable drugs and recommendations for drug dosing should be made based on pharmacological data available for each LMWH.
In recent years, value for money in health care has become of increasing concern. There are various ways to perform an economic evaluation, the most simple being a cost-effectiveness analysis, where differences in costs will influence the choice between methods. Cost-utility and cost-benefit analyses represent more advanced forms of economic evaluations. In this cost-effectiveness analysis, the following three strategies aimed at solving the problem of post-operative thromboembolic complications were compared: (a) no prophylaxis but treatment of occurring complications, (b) general prophylaxis with low-dose heparin for patients over 40 years of age and (c) selective treatment based on post-operative surveillance with a fibrinogen uptake test. Moreover, these alternatives were evaluated for three types of surgery: general abdominal surgery, cholecystectomy and elective hip surgery. Costs for thromboembolic and haemorrhagic complications were estimated from data available for patients hospitalized in Malmö. A sensitivity analysis was made with regard to the frequency of thrombosis, prophylactic effect and treatment costs. Health care costs would be minimized with general prophylaxis in hip and general surgery, whereas no prophylaxis is the most cost-effective alternative in cholecystectomy patients, i.e. with a frequency of thrombosis below 8%. General prophylaxis minimized the duration of patients' health losses due to thromboembolic disease in general, as well as in elective hip surgery. After cholecystectomy, no difference in health loss for the individual was found between the alternative of no prophylaxis and general prophylaxis. Selective treatment was always the least satisfactory alternative in all categories and always the most expensive.
