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Biomedical subjects

L Gunnarsson

Publications and source records attributed to L Gunnarsson.

14 recordsLinked to original sources
PubMed2006

Increased neutrophil membrane expression and plasma level of proteinase 3 in systemic vasculitis are not a consequence of the - 564 A/G promotor polymorphism.

Several findings link proteinase 3 (PR3) to small vessel vasculitis. Besides being a major target of anti-neutrophil cytoplasm antibodies (ANCA), previous findings have shown increased circulating levels of PR3 in vasculitis patients, increased levels of neutrophil membrane-PR3 (mPR3) expression and a skewed distribution of the - 564 A/G polymorphism in the promotor region of the PR3 gene. In this study we elucidate how these three findings relate to each other. The plasma concentration of PR3 was measured by enzyme-linked immunosorbent assay (ELISA), mPR3 expression by fluorescence activated cell sorter (FACS) and the gene polymorphism by real-time polymerase chain reaction (PCR). We compared results from 63 patients with ANCA-associated systemic vasculitis (AASV) with 107 healthy blood donors. In accordance with previous reports, AASV patients had increased plasma concentrations of PR3 compared to healthy controls (mean 224 microg/l versus 155 microg/l, P < 0.0001). They also showed an increased number of mPR3-positive neutrophils (60%versus 42%, P < 0.001). However, contrary to a previous report, we found no skewed distribution of the polymorphism in PR3 gene. There was a weak correlation between mPR3 mean fluorescence intensity (MFI) and plasma PR3 among healthy controls and myeloperoxidase-ANCA (MPO-ANCA)-positive patients (r = 0.24, P = 0.015 and r = 0.52, P = 0.011, respectively). In conclusion, increased plasma PR3 and high expression of mPR3 are associated with small vessel vasculitis, but neither of them is a consequence of the - 564 A/G polymorphism of the PR3 gene promotor.

Case-Control Studies↗
PubMed2004

Epitope mapping of anti-PR3 antibodies using chimeric human/mouse PR3 recombinant proteins.

Autoantibodies against proteinase 3 (PR3) and myeloperoxidase (MPO) (ANCA = anti-neutrophil cytoplasmic antibodies) are used as diagnostic tools for patients with small vessel vasculitis. ANCA are detected by different assays, but the correlation between the results of these assays is generally poor. The overall aim of the study was to provide a framework for the future development of new assays with an increased diagnostic yield. In order to express discrete epitopes of human PR3 (hPR3), the nonantigenic molecules murine PR3 (mPR3) and human leucocyte elastase (HLE) were used as a framework. We constructed recombinant chimeric vectors and were able to produce 6 hPR3/mPR3 proteins and 3 hPR3/HLE proteins. Anti-PR3 monoclonal antibodies differed in their binding pattern to the chimeras, but no distinct binding region could be identified for any monoclonal antibody. The recombinant hPR3/mPR3 were also tested in ELISA with sera from patients with Wegener's granulomatosis with renal involvement. The results show that patients have antibodies to different constructs, indicating that the patients vary in their antibody repertoire from the beginning of the disease, and that patients may have antibodies from a broad range of clones early in the course of the disease. Recombinant hPR3/mPR3 chimeric proteins have a potential to be used as antigens in future ANCA assays.

Amino Acid Sequence↗
PubMed2000

Demonstration of circulating antibodies to Pneumonyssoides caninum in experimentally and naturally infected dogs.

Antibodies to the canine nasal mite, Pneumonyssoides caninum, were demonstrated by ELISA in sera from four experimentally and 77 naturally infected dogs employing a crude P. caninum antigen. In sera from the four experimentally infected dogs, antibodies to P. caninum were first detected on day 11 post-inoculation (p.i.). Optical density (OD) values remained high throughout the observation period of 14 weeks. Two major protein bands with apparent molecular weights of 83 and 74kDa were visible by western blot (WB) from day 11 p.i. On day 14 p.i., another three major protein bands at 44, 37, and 34kDa were visible. The protein pattern then remained essentially constant until the end of the experiment except for some weak bands between 250 and 30kDa which were sometimes visible. In sera obtained from a non-inoculated control dog, no P. caninum antibodies were detected, neither by the ELISA nor by the WB. With sera from 77 naturally infected dogs with a verified diagnosis of P. caninum infection, the OD values varied between 0.24 and 0.95. When sera from four of these dogs were analysed by WB, the protein pattern observed was equivalent with that seen with sera from the experimentally infected dogs on day 25 p.i. Sera from four experimental Beagles, in which no P. caninum mites were found at necropsy, were also analysed by the P. caninum ELISA, the OD values demonstrated never exceeded 0.15. In addition, 48 sera obtained from dogs infected with or allergic to other arthropods were used for studies of possible cross-reactivity. With 10 sera, elevated OD values were found by the ELISA. Eight of them showed a similar banding pattern by the WB as did the experimentally infected dogs on day 25 p.i. This was, therefore, interpreted as an effect of a concurrent P. caninum infection.

Animals↗
PubMed2000

Diseases associated with pronounced eosinophilia: a study of 105 dogs in Sweden.

Records of 105 dogs with pronounced eosinophilia (>2.2 x 10(9) eosinophils/litre) were evaluated in a retrospective study to determine diseases associated with the abnormality in dogs in Sweden. Inflammatory disease in organs with large epithelial surfaces, such as the gut, lungs or skin, was found in 36 per cent of the dogs. A further one-quarter of the 105 cases were placed in the 'miscellaneous' category, which comprised various diseases found at low frequency. The most well defined diagnosis was pulmonary infiltrates with eosinophils in 12 per cent of the dogs. A further 11 per cent had parasitic disease caused by either sarcoptic mange or nasal mite. No atopic dog was found and rottweilers were over-represented in most disease groups. Pronounced eosinophilia, in many cases transient, seems to be associated with a variety of disorders in dogs. In the present study, rottweilers appeared to be more prone to a high eosinophil response than other breeds.

Animals↗
PubMed1998

Experimental infection of dogs with the nasal mite Pneumonyssoides caninum.

A successful experimental transmission of the canine nasal mite, Pneumonyssoides caninum, is described. Some 11 weeks after repeated systemic ivermectin treatment, four Beagles were inoculated via the right nostril with 20 P. caninum mites of different sexes and life stages, obtained at the necropsy of an infected dog. The inoculated dogs and a matching uninoculated control were observed for clinical signs for 14 weeks and then euthanised. Vague upper respiratory signs and a transient minor increase in the number of eosinophils in peripheral blood were recorded in the inoculated dogs. At necropsy 4-12 P. caninum mites were found in the nasal cavities and sinuses of the inoculated dogs, but none in the control. In three out of the four infected dogs mites were found in both the right and left nasal cavities and sinuses of the skull. Since in no case more mites than the number used for inoculation were detected it is not clear if the mites managed to reproduce in the dogs. Inflammatory lesions were seen most consistently in the olfactory mucosa, respiratory mucosa and tonsils, and growth of opportunistic bacteria was observed in the tonsils of the infected dogs. The inflammatory lesions seen in the olfactory mucosa may explain why dogs infected with P. caninum sometimes appear to suffer from impaired scenting ability.

Animals↗
PubMed1996

Influence of age on circulation and arterial blood gases in man.

BACKGROUND: Modern data on the influence of age on hemodynamic and blood gas data in healthy subjects are sparse, especially in middle aged or older subjects. Most measurements have been done in patients during major surgery or in intensive care when the patients have one or more failing organ systems. This study reports on hemodynamics, blood gases and blood volume in healthy patients prior to anesthesia and elective surgery. METHODS: A total of 116 subjects (92 males, 24 females) were investigated prior to anesthesia and elective surgery. No one had received any premedication or was taking regular medication. All subjects were in good physical condition, except for their surgical disease, and clinical examination and history did not reveal any sign of cardiopulmonary disease. Measurements were made of systemic and pulmonary vascular pressures, cardiac output, arterial blood gases and blood volume by 131I-Albumin distribution. RESULTS: Cardiac output, stroke volume, and blood volume correlated to body surface. Relating these variables to body size eliminated almost all differences between the male and female groups. These variables, as well as both systemic and pulmonary artery systolic vascular pressures, were affected by increasing age. Pulmonary capillary wedge and right atrial pressures were not influenced by age. PaO2 decreased with age from 14.0 kPa at 20 years to 11.3 kPa at 80, whereas PaCO2 was unaltered. No effect of light smoking was found on pulmonary circulation or arterial blood gases. Significant correlations were found between blood volume on the one hand and body size and age on the other hand, but not in regard to sex.

Adult↗
PubMed1995

Lung function after open versus laparoscopic cholecystectomy.

Postoperative lung function and gas exchange were studied in 36 patients after cholecystectomy. Twenty-four of the patients underwent laparoscopic cholecystectomy while the remaining twelve were operated with open technique. Before surgery all patients had normal ventilatory volumes (forced vital capacity, FVC and forced expired volume in 1 s, FEV1) and normal gas exchange. Two hours postoperatively FVC was reduced to 64 +/- 16% (P < 0.05) of the preoperative level in the laparoscopic group and to 45 +/- 23% (P < 0.05) after open cholecystectomy. On the first postoperative day FVC was virtually normal in the laparoscopic patients (77 +/- 17% of preoperative level, NS), whereas the open surgery patients still had a decreased FVC (56 +/- 13% of preoperative, P < 0.05). FEV1 in the postoperative period followed the same course as FVC. Gas exchange was significantly impaired in the early postoperative period in all patients but no difference between the two groups was found. Two hours postoperatively PaO2 was reduced to 85% (P < 0.05) of preoperative value and PaCO2 had increased by 0.5 kPa (P < 0.05). The alveolo-arterial oxygen tension difference (PA-aO2) had increased by approximately 45% to a mean of 3.7 kPa (P < 0.05). On the first postoperative day gas exchange was still significantly impaired in the open surgery patients. Atelectasis detected by computed X-ray tomography of the lungs were found in both groups. However, the amount of atelectasis tended to be smaller in the laparoscopic group than in the open surgery patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Atelectasis and lung function in the postoperative period.

Thirteen patients with healthy hearts and lungs, and with a mean age of 68 years, who were scheduled for lower abdominal surgery during isoflurane anaesthesia with muscular paralysis, were investigated with arterial blood gases, spirometry, pulmonary x-ray and computed tomography (CT) of the chest before and during anaesthesia, as well as during the first 4 postoperative days. Before anaesthesia, lung function and gas exchange were normal in all patients. Pulmonary x-ray and CT scans of the lungs were also normal. During anaesthesia, 6 of 13 patients developed atelectasis (mean 1.0% of intrathoracic transverse area in all patients). Two hours postoperatively, 11 of 13 patients had atelectasis and the mean atelectatic area was 1.8%. Pao2 was significantly reduced by 2.1 kPa to 9.8 kPa. On the first postoperative day, the mean atelectasis was unaltered (1.8%). None of the atelectasis found on CT scanning could be detected on standard pulmonary x-ray. Forced vital capacity (FVC) and forced expired volume in 1 s (FEV1) were significantly decreased to 2/3 of preoperative level. Pao2 was significantly reduced to less than 80% of the preoperative level (mean 9.4 kPa). There were significant correlations between the atelectatic area and the impairment in FVC, FEV1, and Pao2. Spirometry and blood gases improved during the succeeding postoperative days, and atelectasis decreased. No patient suffered from pulmonary complications, as judged from clinical criteria and pulmonary x-ray, in contrast to the findings of atelectasis in 85% of the patients by computed tomography.

Abdomen↗
PubMed1991

Influence of age on atelectasis formation and gas exchange impairment during general anaesthesia.

We have studied the effects of anaesthesia on atelectasis formation and gas exchange in 45 patients of both sexes, smokers and nonsmokers, aged 23-69 yr. None of the patients showed clinical signs of pulmonary disease, and preoperative spirometry was normal. In the awake patient, partial pressure of arterial oxygen (PaO2) decreased with increasing age (P less than 0.001) and the alveolar-arterial oxygen partial pressure difference (PAO2-PaO2) increased with age (P less than 0.001). Shunt, assessed by the multiple inert gas elimination technique, was small (mean 0.5%) and uninfluenced by age. However, there was an increasing dispersion (log SD Q) of ventilation/perfusion ratios (VA/Q) and increasing perfusion of regions of low VA/Q (VA/Q less than 0.1) with increasing age (P less than 0.001 and P less than 0.05, respectively). No patient displayed any atelectasis as assessed by computed x-ray tomography of the chest. During inhalation anaesthesia (halothane or enflurane) with mechanical ventilation, 39 of 45 patients developed atelectasis and shunt. There was a strong correlation between the atelectatic area and the magnitude of shunt (r = 0.81, P less than 0.001). Atelectasis and shunt did not increase significantly with age, whereas log SD Q and perfusion of regions with low VA/Q ratios did (r = 0.55, P less than 0.001 and r = 0.35, P less than 0.05, respectively). Awake, the major determinant of PaO2 was perfusion of regions of low VA/Q ratios, which increased with age. During anaesthesia shunt influenced PaO2 most, low VA/Q being a secondary factor which, however, was increasingly important with increasing age, thus explaining the well-known age-dependent deterioration of arterial oxygenation during anaesthesia.

Adult↗
PubMed1991

Anaerobic growth of microorganisms with chlorate as an electron acceptor.

The ability of microorganisms to use chlorate (ClO(3)) as an electron acceptor for respiration under anaerobic conditions was studied in batch and continuous tests. Complex microbial communities were cultivated anaerobically in defined media containing chlorate, all essential minerals, and acetate as the sole energy and carbon source. It was shown that chlorate was reduced to chloride, while acetate was oxidized to carbon dioxide and water and used as the carbon source for synthesis of new biomass. A biomass yield of 1.9 to 3.8 g of volatile suspended solids per equivalent of available electrons was obtained, showing that anaerobic growth with chlorate as an electron acceptor gives a high energy yield. This indicates that microbial reduction of chlorate to chloride in anaerobic systems is coupled with electron transport phosphorylation.

Journal Article↗
PubMed1991

Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment.

Gas exchange impairment and the development of atelectasis during enflurane anaesthesia were studied in 10 patients (mean age 70 yrs) with chronic obstructive pulmonary disease (COPD). Awake, no patient displayed atelectasis as assessed by computed X-ray tomography. The ventilation/perfusion distribution (VA/Q), studied by the multiple inert gas elimination technique, displayed an increased dispersion of VA/Q ratios (the logarithmic standard deviation of the perfusion distribution, mean log Q SD 0.99; upper 95% confidence limit of normal subject: 0.60), and increased perfusion of regions with low VA/Q ratios (0.005 less than VA/Q less than 0.1: 5.4% of cardiac output). Shunt was negligible (mean 0.6%). Computed chest tomography showed significantly larger cross-sectional thoracic areas than previously seen in subjects with healthy lungs (p less than 0.01). No atelectasis was seen in any patient. During anaesthesia there was a further worsening of the VA/Q mismatch with significantly increased log Q SD (1.29, p less than 0.05) but no increase in shunt (mean 1%). Minor atelectatic areas were noted in three patients, the others displayed no atelectasis at all. Chest dimensions were reduced by no more than 3% during anaesthesia, suggesting an unchanged or only minimally affected functional residual capacity. These findings contrast with those seen in patients with healthy lungs in whom atelectasis and shunt regularly develop during anaesthesia.

Aged↗
PubMed1990

Anesthesia for liver transplantation in patients with arterial hypoxemia.

Arterial oxygenation during anesthesia and time of postoperative mechanical ventilation were investigated in 17 patients with chronic liver disease who underwent liver transplantation. Six patients had arterial hypoxemia (PaO2 64 +/- 3 mm Hg) and the other 11 patients had normal PaO2 (105 +/- 5 mm Hg) before transplantation. None of the patients were smokers and all had normal preoperative pulmonary X-ray and spirometry. During transplantation, PaO2 increased in both groups, but PaO2 was still approximately 20% lower and PA-aO2 was 40%-60% higher in the hypoxemic group than in the normoxemic patients (P less than 0.05). The median postoperative time on mechanical ventilation was three times longer in the hypoxemic group (56 h) than in the normoxemic patients (18 h; P = NS). Number or severity of postoperative complications and outcome did not differ between the two groups. It is therefore suggested that patients with arterial hypoxemia without overt lung disease should also be accepted for liver transplantation.

Adolescent↗
PubMed1989

Atelectasis and gas exchange impairment during enflurane/nitrous oxide anaesthesia.

The development of atelectasis and effects on gas exchange during enflurane anaesthesia in nitrogen/oxygen or nitrous oxide/oxygen (inspired oxygen fraction 0.4) were studied in 16 lung-healthy patients (mean age 49 years). Awake, no subject displayed atelectasis as assessed by computed x-ray tomography of the thorax. Pulmonary gas exchange, studied by multiple inert gas elimination technique, and blood gases were normal. After 10 min of enflurane anaesthesia in nitrogen/oxygen, 14 of 16 subjects had developed atelectasis. After 30 min of enflurane anaesthesia in nitrogen/oxygen or nitrous oxide/oxygen, all patients had developed atelectasis, and a further increase was observed after 90 min of anaesthesia to approximately 5% of the intrathoracic area. There was no difference between the two anaesthesia groups. In the nitrogen group, shunt rose to a maximum of 5.8% at 30 min of enflurane anaesthesia, with a significant reduction to the initial anaesthesia level after 90 min of anaesthesia (3.4%). Perfusion of poorly ventilated lung regions (low VA/Q) averaged 4-5% and did not vary significantly during the anaesthesia. In the nitrous oxide group, shunt increased to 6.3% after 90 min of anaesthesia, and there was a parallel decrease in perfusion of low VA/Q regions. The findings suggest that besides prompt collapse of lung tissue during induction of anaesthesia, absorption of gas from closed-off or poorly ventilated regions takes place and further increases the atelectatic area.

Adult↗