Ontology-based, medical domain-specific, use-case driven EMRs for use in clinical quality assurance and passive decision support.

The next evolving stage of the electronic medical records (EMR)--the clinical information system--must be able to support the mental processes involved in clinical reasoning. We have developed a framework for building such systems. By a two step procedure objects are chosen on basis of a process model and described using Unified Modelling Language (UML). UML installs the objects in a middleware-layer between a database and the browser used for presentation. The database and a suggestion of the presentation layout are generated by the middleware. Data entered in the system are provided with a context according to a build in process model. This can be utilized in quality assurance and passive decision support.

[Laparoscopic adrenalectomy. An alternative to open surgery of minor adrenal tumors]. / Laparoskopisk adrenalektomi. Et alternativ til åben operation ved mindre binyretumorer.

In the period February 1994 to November 1995 11 laparoscopic adrenalectomies were performed at our institution (seven women, four men). A transperitoneal approach was used in both right- and left-sided operations. Results were collected retrospectively. Indications for surgery were: Conn's syndrome (four), Cushing's syndrome (two), phaecromocytoma (four), and incidentaloma (one). The operations took median 170 minutes (range 105-250 minutes). Median size of the tumour was 4 cm range 1(1/2)-5 cm). No significant peri- or postoperative complications were recorded. The patients were discharged from the surgical unit median two days after surgery. Laparoscopic operation emerges as an alternative to open operation when dealing with smaller adrenal tumours. Because of the small number of patients, these operations have to be restricted to a few centres where both internists, anaesthesiologists and surgeons with expertise in this field are found.

[Induced sputum. Indication for examination in Pneumocystis carinii pneumonia?]. / Indusert sputum. Indikasjon for undersøkelsen ved Pneumocystis carinii-pneumoni?

Induced sputum is a simple, rapid, and non-invasive technique for detection of Pneumocystis carinii in patients with Pneumocystis carinii pneumonia. In this study 31 patients were examined both with induced sputum and bronchoalveolar lavage. P. carinii was found in 24 patients. In 68% of the samples obtained by the induced sputum method the microorganism was found after Giemsa or methenamine silver staining. In 32% the diagnosis was established in the lavage fluid only. Induced sputum is indicated in moderate cases of P. carinii infection. Bronchoalveolar lavage has to be performed in suspected cases where staining of induced sputum is negative and when coinfection with other microbial agents is suspected.

[Physiotherapy in chronic obstructive pulmonary disease with and without mask training]. / Fysioterapi ved kronisk obstruktiv lungesykdom med og uten masketrening.

16 patients with chronic obstructive lung disease were randomized into two groups which were treated with physiotherapy for six weeks. In one group the treatment also involved using a respiratory training mask. Six patients in both groups completed the study. Both groups experienced an improvement for most parameters. The study showed that physiotherapeutic treatment with physical training improved the patients working capacity. However, the treatment with a mask gave no significant additional effect. 46 outpatients who were treated with a mask were asked later if they still used the mask. Only 28% used it regularly and 35% had stopped using the mask because they did not feel any effect.

[Cold provocation test. A method for diagnosis of bronchial asthma]. / Kuldeprovokasjonstest. En metode for påvisning av bronkial astma.

This article describes the method of isocapnic hyperventilation, where cold air (-22 degrees C) containing 5% CO2 is used to induce a temporary obstruction of airways in patients with bronchial hyperreactivity. The method is quick, has few side effects and is suitable both in the diagnosis and assessment of asthma. Tested out on ten current asthmatics and 14 controls, a median fall in forced expiratory volume (FEV1) of 21.7% was observed in the asthmatic group as against a median fall in FEV1 of 1.4% among the controls.

Amiodarone and thyroid hormone metabolism in the rat heart.

The effect of amiodarone on thyroid hormone metabolism in heart, muscle, liver and kidney was investigated. Rats were treated ip with a high (100 mg.kg-1.day-1) or a low (50 mg.kg-1.day-1) dose of amiodarone for 10 days. Serum T3 was dose-dependently depressed (mean 30 and 54% of controls, respectively, p less than 0.01). rT3 was elevated (to 663 and 313% of controls, p less than 0.01 and 0.05, respectively). Serum T4 was depressed only in the high-dose group (to mean 80%, p less than 0.05). Tissue concentrations of T3 in the heart and muscle from treated animals did not differ from controls, whereas liver and kidney T3 contents were markedly reduced in both groups (p less than 0.05). Heart T4 and rT3 were elevated to about 200% of controls (p less than 0.01 and 0.05, respectively). The same pattern was observed in the other tissues. Iodothyronine-5'-monodeiodinase activity was significantly depressed in all tissues; heart: 32 and 28% of controls (p less than 0.05); muscle: 36 and 49% (p less than 0.01); liver: 11 and 13% (p less than 0.01); kidney: 22 and 28% (p less than 0.01), respectively. In conclusion, amiodarone depresses iodothyronine-5'-monodeiodinase activity in the heart, muscle, liver and kidney in a dose-dependent manner, resulting in lowered T3 concentrations in the liver and kidney, whereas no reduction of tissue T3 content is observed in the heart and muscle. This may indicate that T3 from plasma may cross the cardiac sarcolemma without hindrance.

Faster and more reliable absorption of adrenaline by aerosol inhalation than by subcutaneous injection.

1. The aim of the present study was to compare absorption of adrenaline given by aerosol spray inhalation with absorption after subcutaneous injection. 2. Arterial plasma adrenaline was measured in nine healthy volunteers following adrenaline administration by both methods. 3. Following inhalation of 20 puffs of adrenaline aerosol, 0.15 mg/puff, a peak arterial adrenaline concentration after 1 min and a rapid fall to baseline from this peak occurred. 4. When given by subcutaneous injection absorption was slower with a peak arterial adrenaline concentration after 4 min. The fall in arterial adrenaline from this peak level was not statistically significant within 30 min after injection. 5. There was less intersubject variation of arterial adrenaline concentration following inhalation when compared with injection. 6. Heart rate, blood pressure and finger tremor followed the changes in arterial adrenaline concentrations. 7. These results indicate that absorption is more reliable when adrenaline is given by inhalation. The rapid fall in arterial adrenaline following inhalation, suggests that repeated inhalations are necessary when such adrenaline therapy is required.

Double-blind comparative study of ofloxacin (Hoe 280) and trimethoprim-sulfamethoxazole in the treatment of patients with acute exacerbations of chronic bronchitis and chronic obstructive lung disease.

In a double-blind study of 137 patients with exacerbation of chronic bronchitis and chronic obstructive lung disease, the efficacy and safety of ofloxacin was compared with that of trimethoprim-sulfamethoxazole (TMP/SMX). Both groups improved. The frequency of severe adverse reactions was highest in the TMP/SMX group, and 14.9% of the patients discontinued the treatment. In the ofloxacin group 6% had to stop the treatment. The failure rate was significantly lower in the ofloxacin-treated patients, 3.2% versus 13.8% in the TMP/SMX group. Ofloxacin was found to be an effective drug with few adverse reactions.

Distribution of bronchoalveolar cells and fibronectin levels in bronchoalveolar lavage fluids from patients with lung disorders.

Differential cell counts and fibronectin levels were recorded in bronchoalveolar lavage fluids (BALF) from patients with lung cancer, idiopathic pulmonary fibrosis (IPF), sarcoidosis, pneumonia, acquired immunodeficiency syndrome (AIDS), and chronic obstructive lung disease (COLD). In all groups fibronectin levels were significantly higher than in the control group; patients with sarcoidosis had a six-fold higher fibronectin level (mean values), AIDS 5.4-fold, pneumonia 4.4-fold, lung cancer, IPF and COLD 2.4-3.0-fold. In control smokers the fibronectin level was significantly higher compared to healthy nonsmokers (p less than 0.002). The increased fibronectin levels could not be explained by contamination of BALF with blood or leakage of plasma proteins. Thus, increased fibronectin levels probably reflect local (e.g. macrophage/fibroblast) synthesis.

Renal and glycemic determinants of glomerular hyperfiltration in normoalbuminuric diabetics.

Glomerular hyperfiltration is a characteristic feature of insulin-dependent diabetes. We examined the relative roles of renal size, as well as glycemic parameters (HbA1c, glycosylated albumin, plasma glucose) in addition to growth hormone, somatomedin C, beta-hydroxybutyrate, alanine, and glycerol in determining the glomerular filtration rate (GFR). Sixty-two insulin-dependent patients with normal urinary albumin excretion rates (AER less than 15 micrograms/min), who were less than 50 years of age, were included in the study. Data were subjected to multiple regression analysis with GFR as a dependent variable. Renal volume was the primary statistical determinant of hyperfiltration, but HbA1c also significantly correlated with GFR. No correlation was found with glycosylated albumin or blood glucose, but RPF correlated strongly with GFR, and borderline correlation was found between renal volume and HbA1c. Renal hyperfiltration, defined as a GFR greater than 150 ml/min, was found in approximately 50% of patients with HbA1c values greater than 9.5%. Other studies suggest that such patients have a much higher risk of developing clinically evident diabetic nephropathy over the ensuing years. Renal volume appears to be the major determinant of GFR, but long-term metabolic control, as evidenced by the level of HbA1c, also contributes, partly independent of renal volume. Short-term metabolic control, as evaluated by blood glucose and serum-fructosamine, did not correlate with GFR. We suggest that exact determination of GFR and renal volume should be included in long-term prospective controlled intervention trials in patients with insulin-dependent diabetes mellitus (IDDM).

Early changes in thyroid hormone metabolism in the heart, liver, and brown adipose tissue during the induction of low T3 syndrome in streptozotocin-diabetic rats.

In order to elucidate the day-by-day development of low T3 syndrome, we made rats diabetic by an injection of streptozotocin. Untreated controls killed at day 0 and rats treated for 8 days with insulin after they had received streptozotocin served as controls. Sub-groups of animals were killed 1, 2, 3, 4 and 8 days after streptozotocin. In serum, heart and liver, T3 was depressed to less than 50% of controls at day 4, whereas the insulin-treated rats differed from controls only as to heart T3. Heart iodothyronine 5'-deiodinase activity was depressed to a minimum at day 3 and depression was not prevented by insulin. Liver iodothyronine 5'-deiodinase activity had not reached a minimum at day 8, and again, insulin treatment did not normalize this parameter. T3 contents and iodothyronine 5'-deiodinase activity in brown adipose tissue did not differ from values in controls at any point of time. Thus, in the rats with low T3 syndrome induced by streptozotocin-diabetes, a lowered iodothyronine 5'-deiodinase activity is not fully inhibited by insulin treatment, whereas the T3 content in the liver is re-established during an observation period of 8 days. A direct toxic effect of streptozotocin seems unlikely as an in vitro study showed no influence of streptozotocin on iodothyronine 5'-deiodinase activity in the liver. The study thus indicates that iodothyronine 5'-deiodinase activity in the heart and liver is depressed in experimental diabetes, despite near optimal regulation of blood glucose, and we suggest that lowered intracellular T3 production could, after some time, result in a hypothyroid state in different tissues.

Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract.

The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy.

Local activation of the coagulation and fibrinolysis systems in lung disease.

Extravascular coagulation and fibrinolysis is an integral part of inflammatory reactions. Disordered expression of procoagulant and profibrinolytic factors by mononuclear phagocytes of the lung (i.e. lung alveolar macrophages (LAM) and interstitial macrophages) may have important bearings on inflammatory lung tissue destruction and repair. Based on this hypothesis we have measured the presence of trigger molecules and activation products of the coagulation and fibrinolytic system in cell-free bronchoalveolar lavage fluid and in bronchoalveolar cells. Patient groups with chronic obstructive disease (COLD) (n = 76), idiopathic pulmonary fibrosis (IPF) (n = 29), sarcoidosis (n = 22), lung cancer (n = 36), pneumonia (n = 39), acquired immunodeficiency syndrome (AIDS) (n = 17) and a control group (n = 60) were studied by bronchoalveolar lavage (BAL). In all patient groups tissue thromboplastin (TPL) and fibrinopeptide A (FPA) were significantly increased compared to controls. Plasminogen activator (PA) activity was significantly lower in patients than in normals, and usually associated with high levels of antifibrinolytic activity. The level of PA inhibitor (PAI-2) was not significantly higher in any patient group compared to controls. The sensitivity of the method for fibrin degradation products (FDP) analysis was not high enough to detect FDP in BAL fluid of control individuals, whereas such products could be demonstrated in 25-53% of patients in various categories. We conclude that disordered expression of procoagulant and plasminogen activator activities in bronchoalveolar lavage fluid may reflect a milieu that favours accumulation of fibrin in inflammatory lung tissue and form the basis for the development of pulmonary fibrosis.

Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages.

Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.

Rat heart thyroxine 5'-deiodinase is sensitively depressed by amiodarone.

Thyroxine 5'-deiodinase activity (5'-D) is depressed in rat liver by amiodarone. To investigate the possible tardive effect of amiodarone on 5'-D in different tissues, rats were fed amiodarone according to a short-term (group A, 50 mg amiodarone/kg/day for 10 days, total dose 150 mg, n = 16) and long-term regimen (group B, 25 mg amiodarone/kg/day for 20 days, n = 16) (control group, n = 12). Serum, heart, and other tissues were collected for 10 days after drug cessation. Thyroxine (T4), triiodothyronine (T3), amiodarone, and its active metabolite desethylamiodarone (DEA) were determined in serum, and 5'-D was determined in tissues. In group A, amiodarone concentrations in the heart at the time of drug cessation were two times higher than in group B. Higher amiodarone concentrations were also found in other tissues, and DEA was immeasurable in nearly all tissues at all times. In all tissues the amiodarone content declined rapidly. 5'-D was depressed to about 50% of controls (p less than 0.05) in heart throughout the 10-day observation period, despite unmeasureable drug levels (less than 0.03 microgram/g tissue). In contrast, liver and kidney 5'-D normalized after the first day in both treated groups, while muscle 5'-D did not differ from controls at any time. In conclusion, heart 5'-D seems to be more sensitively depressed by amiodarone than other tissues. Inhibition of thyroid hormone effect in the heart may contribute to the antiarrhythmic properties of amiodarone; however, it cannot be concluded that amiodarone is responsible for the tardive drug effect.

Antigenic specificity of human alveolar macrophages and blood monocytes studied by an immunofluorescence technique.

Lung alveolar macrophages (AM) and blood monocytes (BM) are part of the mononuclear phagocyte system (MPS) and have been shown to be composed of several functionally and biochemically distinct subsets. AM and BM were each fractionated into four subfractions by centrifugation over Percoll, 95 per cent of the monocytes having a higher buoyant density than the high-density AM fraction. Antigen distribution within the cell subfractions was studied by an immunofluorescence technique using a panel of ten monoclonal antibodies (MoAbs) reacting with separate antigenic determinants previously found on mononuclear phagocytes. Several antigens were present on both types of cells (Ki-M1, Ki-M6, Leu-M3, Leu-M5, 1D5, Dako-Ma, and HLA-DR), while other antigens were expressed exclusively on BM (MAS 072 and MAS 081) or on AM (Ki-M8). Ki-M1, Leu-M3, Leu-M5, and HLA-DR were expressed to a greater degree on the surface of AM (95-96 per cent of cells) than on BM (56-68 per cent), while an inverse relationship was noted for 1D5 antigen (present on 41 per cent of BM and 11 per cent of AM). Ki-M6 and Dako-Ma MoAbs recognized an intracellularly restricted antigen present in both AM and BM. Ki-M1, Ki-M8, MAS 072, MAS 081, Leu-M3, Leu-M5, 1D5, and HLA-DR were expressed both in the cytoplasm and at the cell surface. Some antigens (1D5, Leu-M3, MAS 072, MAS 081, and Dako-Ma) showed an uneven distribution among subsets of both AM and BM.(ABSTRACT TRUNCATED AT 250 WORDS)

Tubular handling of neurotensin in the rat kidney as studied by micropuncture and HPLC.

Micropuncture studies were performed to assess the reabsorption and metabolism of the vasoactive peptide neurotensin (NT) in individual nephron segments and compare it to the handling of the closely related peptide bradykinin (BK). Rat proximal and distal convoluted tubules were microinfused with [3H]NT or [3H]BK. In a second set of experiments, [3H]NT and its metabolites in the ureteral urine were separated and characterized using high-performance liquid chromatography (HPLC) technique. The urinary recovery of 3H-labeled material was 31% when proximal tubules were microinfused with [3H]NT and 94% when distal tubules were infused. For proximal tubules the label recovered in the ureteral urine consisted exclusively of metabolites of NT and appeared as tyrosine, NT1-11, probably NT9-13, and two uncharacterized products. For distal tubules, 9% chromatographed as intact NT in the urine and except for the proportion the metabolites were almost identical to those found when proximal tubules were microinfused. Following microinfusion of [3H]BK into proximal tubules, the urinary recovery of 3H-labeled material was 19%. There was no correlation between fractional reabsorption of 3H-labeled material and proximal tubular length when [3H]NT or [3H]BK was microinfused. In vitro incubation studies with rat ureteral urine showed extensive degradation of NT yielding tyrosine, NT1-6, probably NT9-13, NT, and two uncharacterized products. In contrast, there was no detectable breakdown of BK over a 32-min period. Finally, [3H]NT was incubated in rat serum, and these experiments also showed degradation of the peptide but not to the extent as when incubated in ureteral urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Subpopulations of human lung alveolar macrophages: ultrastructural features.

Lung alveolar macrophages (LAM), obtained by bronchoalveolar lavage of healthy donors, were separated into four subfractions on discontinuous gradients of Percoll and subjected to light microscopic, transmission (TEM) and scanning electron microscopic (SEM) studies. Alveolar macrophage morphometric analysis was performed on cytocentrifuged preparations. TEM of subpopulations revealed considerable morphologic heterogeneity. By SEM, cells of the most dense (D) subfraction were small, round, and, typically, the surface was highly ruffled with small membrane pseudopods. Cells of the least dense subfraction (A) showed a low degree of membrane folding or filopodia and were often totally disorganized. In smokers, macrophages of fraction A had a greater area and perimeter compared with non-smokers, whereas the inverse relationship was observed for C and D cells. Also, the number of electron-dense inclusions and the level of acid phosphatase were higher in smokers than in non-smokers. Coupled with functional heterogeneity the morphologic differences described in this paper suggest that density-separated subpopulations of LAM may represent different stages of differentiation or maturation.

Rapid and inexpensive microdetermination of serum fructosamine results in diabetics, uraemics, diabetics with uraemia and healthy subjects.

This paper describes a simple, reliable and inexpensive method for rapid determination of serum fructosamine. The assay is based on commercially available reagents and utilizes equipment accessible in most laboratories (i.e. an automated ELISA-reader interfaced with an IBM computer). In contrast to HbA1c determination, the fructosamine method presented can be used in diabetes complicated by uraemia. In the clinically relevant measuring range, fructosamine is uninfluenced by serum albumin concentration in diabetics with or without uraemia. Eighty microlitres of non-haemolysed capillary serum suffices for a duplicate determination. One year's storage of normal serum induced no change in serum fructosamine estimates. s-Fructosamine in 18 healthy subjects was 2.1 +/- 0.3 mmol/l (mean +/- SD) in venous blood and 2.2 +/- 0.4 mmol/l in capillary blood. In diabetics 3.4 +/- 0.6 mmol/l and 3.3 +/- 0.6 mmol/l (n = 38) were found. The method is well-suited for routine use in the diabetic out-patient clinic.