Implementing security in computer based patient records clinical experiences.

In Norway, organizational changes in hospitals and a stronger focus on patient safety have changed the way of organizing and managing paper based patient records. Hospital-wide patient records tend to replace department based records. Since not only clinicians, but also other non-medical staff have access to the paper records, they also have easy access to all the information which is available on a specific patient; such a system has obvious 'side effects' on privacy and security. Computer based patient records (CPRs) can provide the solution to this apparent paradox if the complex aspects of security, privacy, effectiveness, and user friendliness are focused on jointly from the outset in designing such systems. Clinical experiences in Norway show that it is possible to design patient record systems that provide a very useful tool for clinicians and other health care personnel (HCP) while fully complying with comprehensive security and privacy requirements.

An automated method for the determination of nortriptyline and its isomeric 10-hydroxylated metabolites in plasma by high pressure liquid chromatography.

A high pressure liquid chromatography assay for determination of the tricyclic antidepressant nortriptyline (NT) and its two major metabolites, Z- and E-10-Hydroxy-NT, in plasma is described. Sample preparation included addition of internal standard and a single step extraction procedure. Run time was approximately 14 min. with a LC-18. 5 mu 250 x 4.6 mm column, a mobile phase consisting of aqueous ammonium: methanol: acetonitrile (0.8:6.2:93, v/v), and flow of 1.3 ml/min. NT, Z- and E-10-OH-NT, amitriptyline, Z- and E-10-OH-AT and the internal standard desipramine, were adequately separated within this time span. In our laboratory, the assay has been employed mainly for pharmacokinetic and toxicologic studies in experimental animals at relatively high concentrations.

Distribution of nortriptyline in human blood: effects of temperature, pH, and drug concentration.

An in vitro study of putative factors causing postvenipuncture redistribution of the tricyclic antidepressant nortriptyline (NT) in blood was carried out in blood samples from a single subject. The influence of varying temperature, pH, and drug concentration on the protein binding of NT was assessed by equilibrium dialysis. The influence of the same variables on the distribution of NT in whole blood was measured by calculating the cell/plasma (C/P) drug concentration ratios after centrifugation of blood samples. Variation in temperature did influence the distribution of NT in blood considerably. From 4 to 37 degrees C, the C/P ratio was found to increase from 1.0 +/- 0.1 to 1.7 +/- 0.2, and protein binding expressed as unbound fraction from 2.9 +/- 0.2 to 7.0 +/- 1.1% (mean +/- SD). Neither pH variations within the 7.0-7.6 range, nor variations in drug concentration, were found to alter NT distribution at 37 degrees C. The observed effect of temperature on NT distribution shows that handling of blood samples from patients taking NT should be standardized in order to avoid errors of interpretation.

Metabolic burst and motility in granulocytes following trauma and endotoxinaemia in the anaesthetized pig.

The early effects of trauma and endotoxinaemia in pigs have been studied with regard to granulocyte motility and metabolic burst (chemiluminescence). Increased spontaneous chemiluminescence was observed following a moderate aseptic trauma (osteotomies) or endotoxin infusion in healthy pigs. Zymosan-opsonized chemiluminescence was increased post trauma. Endotoxin infusion, however, led to unchanged values during infusion but a significant decreased Zymosan-opsonized chemiluminescence 3 h after ended infusion. Migration capacity was unchanged by trauma, but markedly reduced following endotoxin infusion. When traumatized pigs had an endotoxin infusion 24 h post trauma, the increase in spontaneous chemiluminescence was significantly more pronounced than following endotoxin infusion in healthy pigs, and Zymosan-opsonized chemiluminescence less decreased. Motility, however, was equally reduced as following endotoxin infusion in healthy pigs. These findings correspond well with the known decreased phagocytic capacity of granulocytes in septicaemia, but also indicate a rapid post-traumatic reaction which might be an attempt to reduce the lethal danger of a subsequent infection.

Effect of hemorrhagic and nortriptyline-induced shock on the porcine pancreas as evaluated by changes in serum cationic trypsin-like immunoreactivity.

Hemorrhagic shock caused by gastrointestinal bleeding in seven pigs and by external bleeding in another six pigs and cardiogenic shock induced by intravenous infusion of the tricyclic antidepressant drug nortriptyline in yet another eight pigs caused a significant increase in serum cationic trypsin-like immunoreactivity together with formation of complexes between cationic trypsin, on the one hand, and alpha-2-macroglobulin and alpha-1-antitrypsin, on the other hand, compatible with what happens in acute pancreatitis.

Release of gastrointestinal hormones in cardiodepressive shock.

In previous studies increased plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin and pancreatic polypeptide (PP) were demonstrated in a porcine endotoxin shock model. Unchanged levels of gastric inhibitory polypeptide (GIP) and secretin point to a specific shock reaction of peptide release and not to a diffuse mucosal leakage. A porcine model of cardiodepressive shock was developed to enable discrimination to be made between a general low-flow state and endotoxin reaction. Infusion of the tricyclic antidepressive agent nortriptyline 15 mg/kg bodyweight resulted in a grave shock state. Increased plasma levels of somatostatin, PP and insulin were found. No increase in VIP levels could be demonstrated. Endotoxin given after nortriptyline administration resulted in the increase of VIP levels regularly seen during endotoxinaemia. VIP release during endotoxin shock is related to endotoxin and not to a general low flow state.

Changes in plasma levels of gastrointestinal regulatory peptides during hemorrhagic shock in pigs.

In an experimental study of hemorrhagic shock, systemic and portal plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin, pancreatic polypeptide (PP), gastric inhibitory peptide (GIP), secretin and insulin were measured with radioimmunoassay methods. Six pigs (30-40 kg) in general anesthesia were submitted to severe hemorrhage (approximately 30% of the blood volume) for 60 min, followed by reinfusion of the shed blood. Aortic blood pressure and cardiac output fell significantly during the shock state and recovered after the infusion. Plasma levels of somatostatin, PP, insulin and secretin rose significantly. The portal levels always presented earlier and greater elevation than did the systemic levels, except as regards secretin. No change was seen in the levels of VIP and GIP.

Increased plasma levels of vasoactive intestinal polypeptide in pigs during endotoxinaemia.

Vasoactive intestinal polypeptide (VIP) is a highly potent vasodilatator. Cardiovascular changes and plasma VIP levels were studied during endotoxinaemia (Escherichia coli endotoxin 1 mg/kg) in a carefully monitored porcine model. Endotoxin infusion resulted in a profound but reversible shock and a substantial rise in plasma VIP levels. Increased levels of VIP could be demonstrated already after 30 min of endotoxin infusion and increased further during the infusion. Animals followed for a period of 60 h demonstrated slowly declining levels of VIP after endotoxin infusion but significantly elevated levels were usually found 24 h after infusion. Control animals did not show any changes in VIP during a similar procedure. Release of gastrointestinal peptides may be of importance during septic shock.

Tissue thromboplastin generation in circulating mononuclear phagocytes and development of coagulation disorders during E. coli endotoxinaemia in pigs.

Tissue thromboplastin generation in monocytes was studied during various stages of Escherichia coli endotoxinaemia in pigs. The pigs were monitored in halothane anaesthesia and mechanically ventilated. Blood was sampled from the superior caval vein before and during endotoxin infusion and up to 6 hours after its start. Monnuclear leukocytes were harvested with Lymphoprep separation and monocyte counts were made, using TRITC-labelled sheep erythrocytes, acridine orange and a fluorescence microscope. Thromboplastin was quantified in a two-stage assay by incubating the test sample together with purified factor X, factor VII and Ca++. The generated factor Xa was thereafter assayed. There was statistically significant increase of tissue thromboplastin activity in monocytes after endotoxin infusion. Maximum level was reached at the end of the infusion and was maintained throughout the observation period. Decrease occurred in platelets, leukocytes, antithrombin III, fibrinogen and clotting factors V, VII and VIII, and clotting time was prolonged. These findings indicated significant disseminated intravascular coagulation. The endotoxin-stimulated monocytes with their elevated tissue thrombo-plastin activity thus may play an important part in development of the DIC which so often follows septicemia.

Release of gastrointestinal peptides during E. coli endotoxinaemia.

We have earlier reported an elevation of vasoactive intestinal polypeptide (VIP) plasma levels during endotoxinaemia in pigs (Revhaug et al., 1983). In the present study the plasma levels of pancreatic polypeptide (PP), somatostatin, gastric inhibitory peptide (GIP) and insulin have been measured by sensitive Ria methods during E. coli endotoxin (Difco) shock in six anaesthetized pigs. The plasma samples were drawn from the vena porta, cava superior, internal jugular vein and the aorta. A significant increase in plasma levels of PP, somatostatin, and insulin was observed in this model. The increased plasma levels were higher in the portal vein than in the other sampling site. GIP did not present any change in this model.

Lysosomal hydrolases in neutrophils, mononuclear cells and serum during Escherichia coli endotoxinaemia in pigs.

The appearance of 10 different lysosomal enzymes in leucocytes and serum were studied during various stages of Escherichia coli endotoxinaemia in pigs. The animals were monitored in halothane anaesthesia and ventilated with a mechanical ventilator. The endotoxin infusion induced a marked increase in pulmonary artery pressure while the systemic blood pressure was significantly lowered. A pronounced decline in circulating leucocytes occurred. There was a general trend of intracellular reduction of lysosomal enzymes in both PMN and mononuclear cells, whereas increasing serum levels of the same enzymes occurred. Significantly higher serum levels of all lysosomal enzymes were found 5 h after start of endotoxin infusion compared to preinfusion values, while a significant acidosis in the aorta blood was registered. These results indicate that lysosomal enzymes are released from white blood cells following endotoxin stimulation. When local pH values allow enzyme activity, they may contribute to the tissue destruction seen in endotoxinaemia.

Controlled endotoxinemia in pigs. A suitable model for in vivo studies of some haemodynamic, humoral and cellular reactions.

To study the haemodynamic, cellular and humoral changes seen during septicemia-endotoxinemia a relatively large animal is needed. Pigs are satisfactory in size but have a tendency to develop malignant hyperthermia reaction to stress situations and certain anaesthetic agents. This problem was solved using a screening test of halothane exposure. When later used for experiments, the nonresponding pigs developed the typical hypokinetic low-flow state after endotoxin challenge seen in the advanced stage of septicemia in man. Decreased number of circulating leucocytes and platelets, increased tissue thromboplastin production in monocytes, and a significant coagulation disorder (DIC) were observed. Release of oxygen radicals and lysosomal enzymes from leucocytes could be estimated. Endotoxin levels in plasma were easily measured. This pig model of controlled endotoxinemia correlates well with some important haemodynamic, cellular and humoral reactions observed during human in vivo observations and in vitro studies. This model may thus be a valuable tool in clinical research of endotoxinemia and septicemia.

A sensitive gas chromatographic assay for amitriptyline and nortriptyline in plasma.

A method for the quantitative determination of the tricyclic antidepressant drug amitriptyline (AT) and its active major metabolite, nortriptyline (NT), in plasma is described. The method involves a three-step extraction procedure, no derivatization, and a rapid run on a gas--liquid chromatograph equipped with a nitrogen detector. The standard curves were linear in the range of 25-1,000 ng/ml. The lower detection limit was 2-5 ng/ml for both drugs. The method is specific for AT and NT, with a recovery of AT and NT of 68 and 71%, respectively. The precision of the method, expressed as the coefficient of variation, was 10.7% for AT and 12.9% for NT within 25--1,000 ng/ml. The method has proven to be suitable for monitoring plasma levels of AT and NT in patients, and in animals during experimental studies on pharmacokinetics after therapeutic and toxic doses of NT.

Essential features of a criterion-based, integrated examination at Tromsø, Norway.

With data from the first integrated examinations at Stage II in the medical curriculum at Tromsø, Norway, we have found that essay-type sequential case problems may be designed according to the pattern described as 'Patient Management Problems'. In particular, a new 'standardized' morphology problem which is labour-saving and which demands from the respondents general skills of high relevance was created. We also found that the taxonomic level of this comprehensive and integrated examination could be raised by following a few simple suggestion. The reliability of the examination is shown to be above average, when pre-accepted model answers are use throughout. New criterion-sets describing clearly acceptable and clearly non-acceptable performances (established by finding the 99% safety limits of the chosen minimum passing level, taking the number of samples into account) were applied prospectively in 1978. Of 42 candidates 37 were classified as clearly passing, while three were classifed as having failed. The validity of the sets was evaluated by using them retrospectively on the 1977 data. It was shown that they were then able to pick out as failures the same four student whom the board had filed in 1977. The format has been favourably received by both students and teachers.