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Biomedical subjects

A Johansson

Publications and source records attributed to A Johansson.

At least 127 records · Page 7Linked to original sources
PubMed2000

Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia.

PCR and culture were comparatively evaluated for their abilities to demonstrate Francisella tularensis in wound specimens from tularemia patients during an outbreak in Sweden in 1998. For transport of the specimens used for PCR, a buffer solution containing a nuclease inhibitor was used, and for transport of the specimens used for culture, a commercial transport system was selected after experimental comparison of various systems. Of 40 patients with culture- and/or serology-verified ulceroglandular tularemia, PCR detected F. tularensis DNA in 30 (75%) patients, whereas culture detected bacterial growth in 25 (62%) patients. Compared to data from a previous study, the present inclusion of a nuclease inhibitor in the transport medium did not improve the sensitivity of the PCR, whereas the sensitivity of the culture procedure was significantly increased by selection of the system used for transport. Among eight patients with clinically suspected tularemia but with negative serology and culture, specimens from four patients showed detectable DNA. In three of these patients the diagnosis was verified by the demonstration of an F. tularensis-specific T-cell response in vitro. In conclusion, PCR was more sensitive than culture for demonstration of F. tularensis in wound specimens. Besides, we showed that tularemia may proceed without development of serum antibodies, and in these patients, PCR may be of special importance for verification of the diagnosis.

Adult↗
PubMed2000

Evaluation of PCR-based methods for discrimination of Francisella species and subspecies and development of a specific PCR that distinguishes the two major subspecies of Francisella tularensis.

Previous studies have demonstrated that the four subspecies of the human pathogen Francisella tularensis, despite showing marked variations in their virulence for mammals and originating from different regions in the Northern Hemisphere, display a very close phylogenetic relationship. This property has hampered the development of generally applicable typing methods. To overcome this problem, we evaluated the use of PCR for discrimination of the subspecies using various forms of long arbitrary primers or primers specific for repetitive extragenic palindromic sequences (REP) or enterobacterial repetitive intragenic consensus (ERIC) sequences. Patterns generated by use of REP, ERIC, or long arbitrary primers allowed differentiation at the species level and of the four subspecies of F. tularensis. With each of these three methods, similar or identical clustering of strains was found, and groups of strains of different geographical origins or differing in virulence showed distinct patterns. The discriminatory indices of the methods varied from 0.57 to 0.65; thus, the patterns were not sufficiently discriminatory to distinguish individual strains. The sequence of a fragment generated by amplification with an arbitrary primer was determined, and a region showing interstrain heterogeneity was identified. Specific primers were designed, and a PCR was developed that distinguished strains of F. tularensis subsp. holarctica from strains of other F. tularensis subspecies, including strains of the highly virulent F. tularensis subsp. tularensis. Notably, one European isolate showed the genetic pattern typical of the highly virulent F. tularensis subsp. tularensis, generally believed to exist only in North America. It is proposed that a combination of the specific PCR together with one method generating subspecies-specific patterns is suitable as a rapid and relatively simple strategy for discrimination of Francisella species and subspecies.

DNA Primers↗
PubMed2000

Moral sensitivity: some differences between nurses and physicians.

We report the results of an investigation of nurses' and physicians' sensitivity to ethical dimensions of clinical practice. The sample consisted of 113 physicians working in general medical settings, 665 psychiatrists, 150 nurses working in general medical settings, and 145 nurses working in psychiatry. The instrument used was the Moral Sensitivity Questionnaire (MSQ), a self-reporting Likert-type questionnaire consisting of 30 assumptions related to moral sensitivity in health care practice. Each of these assumptions was categorized into a theoretical dimension of moral sensitivity: relational orientation, structuring moral meaning, expressing benevolence, modifying autonomy, experiencing moral conflict, and following the rules. Significant differences in responses were found between health care professionals from general medical settings and those working in psychiatry. The former agreed to a greater extent with the assumptions in the categories 'meaning' and 'autonomy' and to a lesser degree with the categories 'benevolence' and 'conflict'. Moreover, those from the psychiatric sector agreed to a greater extent to the use of coercion if necessary. Significant differences were also found for some of the MSQ categories, between physicians and nurses, and between males and females.

Ethics, Medical↗
PubMed2000

Rat alveolar and interstitial macrophages in the fibrosing stage following quartz exposure.

Exposure to quartz induces pulmonary inflammation and development of fibrosis. In order to study the fibrosing process, we investigated morphology, function and phenotype of alveolar (AMs) and interstitial (IMs) macrophages at an early stage of fibrosis in rats. Rats were exposed by intratracheal instillations of 10 mg quartz (n=8) or saline (n=8) and studied 3 months later. AMs were obtained by bronchoalveolar lavage and IMs by mechanical fragmentation, followed by enzymatic digestion of lung tissue. Histology revealed subacute silicosis, with early focal fibrosis and alveolar lipoproteinosis. AM quartz exposure increased phagocytic activity and expression of major histocompatibility complex (MHC) Ia antigens, the latter being associated with cellular antigen presenting capacity. IM had an even more pronounced expression of MHC than AM after quartz exposure. Both macrophage fractions had a higher expression of OX-42 (complement receptor 3, CR3) than controls, but the increase in the IM fraction might be explained by the remaining AM in the IM fraction. Exposed AM adhered less to extracellular matrix components (vitronectin and fibronectin) than controls. In contrast, the adhesion of IM to vitronectin increased after exposure. Besides increased adhesion, the effects on IM were scarce. Our results therefore do not support the hypothesis that IM has a key role in the process of inflammation, including fibrosis.

Animals↗
PubMed2000

Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy.

Metabolic-endocrine dysfunctions, including hyperinsulinemia, hypertriglyceridemia, increased fat mass, and dysregulation of the hypothalamic-pituitary-adrenal axis, are common in myotonic dystrophy (MD). We hypothesized that increased production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may be important underlying mechanisms. We studied the diurnal rhythmicity of cytokines and cortisol, ACTH, and dehydroepiandrosterone in 18 men with adult onset MD and 18 controls. Morning levels of androstenedione, 17-hydroxyprogesterone, testosterone, and insulin were also determined. Genetic analyses were performed, including calculation of allele sizes. Median circulating 24-h levels of IL-6 (P < 0.001), TNF-alpha (P = 0.05), ACTH (P < 0.05), and cortisol (P < 0.05) were all significantly increased in MD, whereas dehydroepiandrosterone levels were decreased (P < 0.001). The diurnal rhythms of these cytokines/ hormones were disturbed in patients. Morning testosterone levels were decreased and insulin levels increased (P < 0.01 for both). Patients with high body fat mass had significantly increased insulin levels and decreased morning levels of cortisol, ACTH, and testosterone. IL-6 and TNF-alpha levels are increased and adrenocortical hormone regulation is disturbed in MD. Adiposity may contribute to these disturbances, which may be of importance for decreased adrenal androgen hormone production and metabolic, muscular, and neuropsychiatric dysfunction in MD.

Adipose Tissue↗
PubMed2000

The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1.

A mammalian homologue of the PDZ domain containing Caenorhabditis elegans protein PAR-6 was found in a yeast two-hybrid system screen as binding to the Rho family member Cdc42. PAR-6 contains a PDZ domain and in C. elegans it has been shown to be crucial for the asymmetric cleavage and establishment of cell polarity during the first cell divisions in the growing embryo. Mammalian PAR-6 interacted with Cdc42 and Rac1 both in the yeast two-hybrid system and in in vitro binding assays. Co-immunoprecipitation experiments, employing transiently transfected Cos-1 cells, further confirmed that Cdc42 and Rac1 are physiological binding partners for PAR-6. We found that, in epithelial Madin-Darby canine kidney cells (MDCK), endogenous PAR-6 was present in the tight junctions, as judged from its co-localisation with the tight junction protein ZO-1, however, PAR-6 was also detected in the cell nucleus. Stimulation of MDCK cells with scatter factor/hepatocyte growth factor induced a loss of PAR-6 from the areas of cell-cell contacts in conformity with their progressive breakdown. In C. elegans PAR-6 co-localises with PAR-3 and has been suggested to form a direct complex. In agreement with earlier studies, mammalian PAR-3 was found to be present in tight junctions of MDCK cells but, in contrast to PAR-6, the protein could not be detected in the nucleus. Furthermore, co-immunoprecipitation experiments, employing Cos-1 cells, demonstrated that mammalian PAR-6 and PAR-3 formed a direct complex. These findings, together with the reported roles of PAR-6 and PAR-3 in C. elegans, suggest that Cdc42 and Rac1 and PAR-6/PAR-3 are involved in the establishment of cell polarity in epithelial cells.

Animals↗
PubMed1999

Epitope specificity of the monoclonal anticytokeratin antibody TS1.

Due to their abundance in epithelial cells and deposition in necrotic regions intratumorally, cytokeratins (CKs) have been established as valuable targets for both radioimmunolocalization and radioimmunotherapy. The target epitope for the monoclonal anti-CK8 antibody, TS1, used for both experimental radioimmunolocalization and radioimmunotherapy, was determined by means of synthesis of 96 overlapping peptides that covered the entire CK8 molecule. A highly conserved peptide sequence, spanning amino acids (aa) 343-357 and covering the discontinuous epitope in the helical 2B domain, was identified. The epitope retains its helical structure, as shown with circular dichroism spectroscopy, although the length of the peptide (ie., >20 aa) is crucial for maintenance of immunoreactivity. To determine which aa residues are crucial for binding to the monoclonal antibody, alanine scanning was performed on a 26-mer covering aa 340-365, with the sequence QRGELAIKDANAKLSELEAALQRAKQ. The 26 modified peptides were evaluated using ELISA and BIAcore technology. The uniqueness of this epitope has been established by data base sequence comparisons.

Amino Acid Sequence↗
PubMed1999

Ingested aggregates of ultrafine carbon particles and interferon-gamma impair rat alveolar macrophage function.

Alveolar macrophages (AM), obtained by lavage from the rat lung, were allowed to ingest aggregated ultrafine carbon particles, about 1 microgram/10(6) AM, which is a realistic result of long-term exposure to ambient air. The effects of the ingested carbon on the phagocytosis of test particles and oxidative metabolism of the AM were studied. In addition, the effects of short-term (40 min or 2 h) and long-term (28 or 44 h) incubation with interferon gamma (IFN-gamma) on AM loaded and unloaded with carbon were investigated. Phagocytic activity was studied using fluorescein-labeled 3.2-microgram silica particles. The attachment and ingestion processes were evaluated separately. The ingested carbon markedly impaired the phagocytosis of silica particles; the accumulated attachment (sum of attached and ingested particles per AM) decreased from 5.0 to 4.2 particles/AM and the ingested fraction (number of ingested particles per AM divided with accumulated attachment) from 0.42 to 0.27. The short-term incubation with IFN-gamma tended to increase the accumulated attachment (from 5.0 to 5.7 particles/AM) and decreased the ingested fraction (from 0.42 to 0.34) in unloaded AM. Long-term incubation with IFN-gamma markedly impaired both the accumulated attachment (to 3.8 particles/AM) and the ingested fraction (to 0.24) in unloaded AM and the carbon load further decreased the accumulated attachment to 2.8 particles/AM, and the ingested fraction to 0.21. The oxidative metabolism was not effected by the ingested carbon or the short-term incubation with IFN-gamma, but the long-term incubation with IFN-gamma increased it with a factor of almost 3. Our results suggest that ingested environmental particles in AM may markedly impair their phagocytic capacity, especially during long-term exposure to IFN-gamma as after infections, and there might be an increased risk for additional infections. Moreover, during an episode of high ambient particle concentration the inhaled particles will not be efficiently phagocytized and may thereby damage the Lung tissue.

Air Pollution↗
PubMed1999

Estimation of respiratory volumes from the photoplethysmographic signal. Part I: Experimental results.

To evaluate the possibility of respiratory-volume measurement using photoplethysmography (PPG), PPG signals from 16 normal volunteers are collected, and the respiratory-induced intensity variations (RIIV) are digitally extracted. The RIIV signals are studied while respiratory volume is varied. Furthermore, respiratory rate, body posture and type of respiration are varied. A Fleisch pneumotachograph is used as the inspired volume reference. The RIIV and pneumotachograph signals are compared, and a statistical analysis is performed (linear regression and t-tests). The key idea is that the amplitude of the RIIV signal is related to the respiratory volume. The conclusion from the measurements is that there exists a relationship between the amplitude of the RIIV signal and the respiratory volume (R = 0.842, s = 0.428, p < 0.005). Absolute measurements of the respiratory volume are not possible from the RIIV signal with the present set-up. The RIIV signal also seems to be affected by respiratory rate and type. More knowledge about respiratory parameters and improved sensor and filter design are required to make absolute measurements of volumes possible.

Adult↗
PubMed1999

Estimation of respiratory volumes from the photoplethysmographic signal. Part 2: A model study.

A Windkessel model has been constructed with the aim of investigating the respiratory-volume dependence of the photoplethysmographic (PPG) signal. Experimental studies show a correlation between respiratory volume and the peak-to-peak value of the respiratory-induced intensity variations (RIIV) in the PPG signal. The model compartments are organised in two closed chambers, representing the thorax and the abdomen, and in a peripheral part not directly influenced by respiration. Cardiac pulse and respiration are created by continuous adjustment of the pressures in the affected compartments. Together with the criteria for heart and venous valves, the model is based on a set of 17 differential equations. These equations are solved for varying thoracic and abdominal pressures corresponding to different respiratory volumes. Furthermore, a sensitivity analysis is performed to evaluate the properties of the model. The PPG signals are created as a combination of peripheral blood flow and pressure. From these signals, the respiratory synchronous parts are extracted and analysed. To study some important limitations of the model, respiratory type and rate are varied. From the simulations, it is possible to verify our earlier experimental results concerning the relationship between respiratory volume and the peak-to-peak value of the RIIV signal. An expected decrease in the amplitude of the respiratory signal with increased respiratory rate is also found, which is due to the lowpass characteristics of the vessel system. Variations in the relationship between thoracic and abdominal respiration also affect the RIIV signal. The simulations explain and verify what has been found previously in experimental studies.

Computer Simulation↗
PubMed1999

Material and design in haematogenous implant-associated infections in a rabbit model.

We used 111 rabbits to study the susceptibility to intravenously injected bacteria of conventional stainless steel plates, and titanium plates of either traditional design or of the PC-FIX concept, that is less traumatic to bone. After plating, the animals were given between 1 x 10(8) and 2 x 10(9) colony forming units of Staphylococcus aureus Wood 46 intravenously. Significant differences in infection rates (positive cultures) were found between conventional stainless steel plates (36-67% infected, depending on inoculum size) and titanium PC-FIX plates (6-7% infected). In fact, the infection rate at the PC-FIX plate did not differ from sham operated animals. Since conventionally designed titanium plates had an intermediate infection rate, it appears that design and material both are important for the risk of infection.

Animals↗
PubMed1999

Local plate infections in a rabbit model.

We used 30 New Zealand white rabbits to compare the susceptibility to bacterial challenge of two different orthopaedic implants: a standard-design stainless steel plate, or a PC-FIX titanium plate applied on the right tibia were compared with sham operated animals. Directly after surgery Staphylococcus aureus (10(8)-10(9) colony forming units) were inoculated close to the plate. The infection rate in the group of plated animals was 11/20 (stainless steel plates 6/10, PC-FIX titanium plates 5/10) and in sham operated animals only 1/10. Thus, a foreign body increased the risk for infection (p = 0.02). However, the implant type did not appear to be of major importance when the bacteria were inoculated locally. In experimental haematogenous infections, by contrast, implant design and material are considered to be important. This may either indicate different pathogenic mechanisms in locally and haematogenously induced infections, or simply that the large number of microorganisms in local inoculation 'overload' the normal defence systems.

Animals↗
PubMed1999

Monitoring of heart and respiratory rates in newborn infants using a new photoplethysmographic technique.

OBJECTIVE: A new photoplethysmographic (PPG) device for respiratory and heart rate monitoring has been evaluated in the neonatal care units at the University Children's Hospital of Uppsala, Sweden. The purpose of this study was to compare this new device with more established techniques, i.e., transthoracic impedance plethysmography (TTI) for monitoring of respiratory rate and ECG for heart rate monitoring. METHODS: Data were acquired continuously for 8-hours in each of 6 neonates. The signals were analysed for periods of 30 seconds, in which the heart and respiratory signals from the PPG device were compared with the ECG and the impedance plethysmogram. RESULTS: The ECG recordings were of high quality in 77% of the analysed periods. In these periods, excluding periods (6%) disturbed by offset-adjustement of the PPG signal, the PPG heart signal included 1.1% (+/- 0.7% SD) false negative beats and 0.9% (+/- 0.6%) false positive beats. In periods with an impedance signal of high quality (29% of total time), the part of the PPG signal synchronous with respiration included 2.7% (+/- 1.1%) false negative breaths and 1.5% (+/- 0.4%) false positive breaths. Here, 2% of the periods were discarded because of offset-adjustment. From the periods of low signal quality, two other conclusions were drawn: 1) The impedance signal contains more power in the respiratory range than the corresponding PPG respiratory signal. 2) The breaths are easier to identify in the PPG respiratory signal than in the impedance signal (subjective measure). CONCLUSIONS: Electrode and motion artefacts seem to disturb the ECG signals and, particularly, the impedance signals. During periods of high quality ECG and impedance signals, the new optical device produces signals of equal quality to these traditional methods, and is in some cases even better. The new device is non-invasive and has a small optical probe. These factors indicate further advantages of the photoplethysmographic method.

Electric Impedance↗
PubMed1999

An independent association between obstructive sleep apnoea and coronary artery disease.

Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Skövde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.

Adult↗
PubMed1999

Adrenal steroid dysregulation in dystrophia myotonica.

OBJECTIVE: To evaluate circulating adrenal steroid hormones, cortisol diurnal rhythm and the negative feedback function of the cortisol axis in patients with dystrophia myotonica (DyM), a disease where metabolic disturbances, peripheral insulin insensitivity and cognitive dysfunction are common features. DESIGN: Morning serum levels of dehydroepiandrosterone sulphate, androstenedione, 17 alpha-hydroxy progesterone and cortisol; morning serum levels of testosterone and insulin; diurnal rhythm of saliva cortisol; and an overnight dexamethasone suppression test, together with a cognitive screening test in men with DyM and in controls. SETTING: Outpatient clinic in co-operation with Umeå University Hospital. SUBJECTS: Fifteen men with DyM and 13 age-matched controls. MAIN OUTCOME MEASURES: Adrenal steroid hormone levels, diurnal rhythm of saliva cortisol, dexamethasone suppression test and Mini Mental State Examination scores. RESULTS: Morning serum levels of dehydroepiandrosterone sulphate, androstenedione and 17 alpha-hydroxy progesterone were significantly decreased in DyM after inclusion of age and body mass index in multiple regression analyses (48, 26 and 32% decreases, respectively). An abnormal diurnal rhythm of saliva cortisol was present in all patients, mean saliva cortisol levels being significantly increased (33%) in DyM patients. Dexamethasone suppressibility did not differ between groups. DyM patients scored significantly lower on the Mini Mental State Examination (P < 0.001). CONCLUSIONS: These results indicate an abnormal adrenal steroid hormone secretion in DyM, which may contribute to peripheral insulin sensitivity as well as cognitive impairment in these patients.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Pharmacokinetics of latanoprost in the cynomolgus monkey. 3rd communication: tissue distribution after topical administration on the eye studied by whole body autoradiography. Glaucoma Research Laboratories.

Latanoprost (13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2 alpha-isopropyl ester, CAS 130209-82-4, PhXA41, Xalatan), an antiglaucoma drug, labelled with tritium at carbon 13 and 14 (4.8 micrograms, 20.8 MBq/eye) was administered topically on the eyes of cynomolgus monkeys. After 0.5 h the concentration of radioactivity in the cornea was estimated to be about 0.6 ng eq/mg tissue. The elimination half-life of total radioactivity in the cornea was about 4 h. The corneal epithelium contained a higher concentration of radioactivity than the stroma. Cornea seemed to act as a slow release depot to the anterior part of the eye. In the iris, anterior chamber and ciliary body the maximal concentrations were 217.0 +/- 12.9 pg eq/mg, 99.8 +/- 7.4 pg eq/mg and 54.0 +/- 4.9 pg eq/mg, respectively, 1 h after administration. The elimination half-life of total radioactivity from these tissues was 3-4 h. Trace amounts (0.4-9 pg eq/mg) remained in these tissues 24 h after administration. Initially the radioactivity was present in the conjunctiva, sclera and choroid as well as in the general circulation. Radioactivity passed through the lachrymal ducts and high concentrations were observed in the oesophagus, stomach content, small intestine, bile and urine of a monkey administered latanoprost topical on the eye 0.5 and 1 h before sacrifice. In this animal concentrations of radioactivity were found in the kidney, liver, wall of the small intestine and blood. All other tissues in this animal contained lower concentrations of radioiactivity than the blood. In an animal sacrificed 2 h after administration of tritium labelled latanoprost on one eye and 6 h after administration on the other eye the highest concentrations of radioactivity were found in urine, bile and in the stomach content. Low concentration of radioactivity remained in the kidney and the liver. In a monkey administered latanoprost 12 and 24 h before death low concentrations remained in the colon, bile and urine. The anterior parts of the eyes from the monkey sacrificed 0.5 and 1 h after administration of latanoprost were cut out from the tissue sections for HPLC analysis. The predominating peak present corresponded to acid of latanoprost (PhXA85). In the stomach the radioactivity chromatographed as latanoprost and the acid of latanoprost. In the small intestine and in bile the main radioactive peak corresponded to 1,2-dinor-acid of latanoprost and in addition several more polar metabolites were present. In conclusion, latanoprost penetrated the cornea, was hydrolysed and slowly released into the anterior parts of the eye the site of action. The maximum concentration in the eye was reached after 1 h with an elimination half-life of 3-4 h. In the body the distribution was limited mainly to the gastro-intestinal tract, the kidney, the gall- and urinary bladder.

Administration, Topical↗