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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 109 records · Page 6Linked to original sources
PubMed2000

Kinetic properties of missense mutations in patients with glutathione synthetase deficiency.

Patients with hereditary glutathione synthetase (GS) (EC 6.3.2.3) deficiency present with variable clinical pictures, presumably related to the nature of the mutations involved. In order to elucidate the relationship between genotype, enzyme function and clinical phenotype, we have characterized enzyme kinetic parameters of missense mutations R125C, R267W, R330C and G464V from patients with GS deficiency. One of the mutations predominantly affected the K(m) value, with decreased affinity for glycine, two mutations influenced both K(m) and V(max) values, and one mutation reduced the stability of the enzyme. This characterization agrees well with predictions based on the recently reported crystal structure of human GS. Thus our data indicate that different mutations can affect the catalytic capacity of GS by decreasing substrate affinity, maximal velocity or enzyme stability.

Chromatography, Agarose↗
PubMed2000

[Ventilation in ARDS: respirator, prone position, NO or artificial lung].

This review discusses the treatment of impaired gas exchange in acute respiratory distress syndrome (ARDS) using conventional ventilation, the open lung approach, prone position, nitric oxide (NO) inhalation and extracorporeal membrane oxygenation (ECMO). It is concluded that ventilation with high inspiratory pressures or volumes should be avoided, and that the open lung approach should be used as the first step. If this does not lead to satisfactory results, prone positioning is recommended, and if life-threatening hypoxemia persists, ECMO could be considered. NO inhalation is not recommended.

Adult↗
PubMed2000

A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia.

gamma-Glutamylcysteine synthetase (GCS) catalyzes the initial and rate-limiting step in the biosynthesis of glutathione. gamma-GCS consists of a heavy and a light subunit encoded by separate genes. Hereditary deficiency of GCS has been reported in 6 patients with hemolytic anemia and low erythrocyte levels of glutathione and gamma-glutamylcysteine. In addition, 2 patients also had generalized aminoaciduria and developed neurologic symptoms. We have examined a Dutch kindred with 1 suspected case of GCS deficiency. The proband was a 68-year-old woman with a history of transient jaundice and compensated hemolytic anemia. One of her grandchildren was also GCS deficient; he was 11 years old and had a history of neonatal jaundice. The enzyme defect was confirmed and GCS activity was found to be less than 2% of normal in the erythrocytes of both patients. The complementary DNA (cDNA) for the heavy subunit of GCS was sequenced in these patients and in several members of the family. The proband and her GCS- deficient grandson were identified as homozygous for a 473C-->T substitution, changing codon 158 from CCC for proline into CTC for leucine. Several family members with half-normal GCS activity in their erythrocytes were heterozygous for the mutation.

Aged↗
PubMed2000

A new device for 100 per cent humidification of inspired air.

STATEMENT OF FINDINGS: A new humidifier for use during mechanical ventilation in endotracheally intubated patients is described and tested. The humidifier is based on a heat-moisture exchanger, which absorbs the expired heat and moisture and releases it into the inspired air. External heat and water are then added at the patient side of the heat-moisture exchanger, so that the inspired gas should reach 100% humidity (44 mg/l) at 37 degrees C. In bench tests using constant and decelerating inspiratory flow and minute volumes of 3-25 l the device gave an absolute humidity of 41-44 mg/l, and it reduced the amount of water consumed in eight mechanically ventilated patients compared with a conventional active humidifier. During a 24-h test period there was no water condensation in the ventilator tubing with the new device.

Critical Care↗
PubMed2000

DNA adducts in perch (Perca fluviatilis) living in coastal water polluted with bleached pulp mill effluents.

DNA adducts were analyzed by (32)P-postlabeling in liver and intestine of perch (Perca fluviatilis). Fish were collected in the receiving water of a bleached kraft pulp mill at Norrsundet, Sweden, on the coast of the Bothnian Sea, and in three different reference areas. Sampling was carried out the last week in September 1993, 1995, and 1997. Since 1984/1985 the pulping process at Norrsundet has been successively modified and an external waste-water treatment has been installed, resulting in lowered and altered effluent discharges. Nevertheless, perch captured in the water area closest to the mill (2 km) had significantly elevated levels of aromatic/hydrophobic DNA adducts in both liver and intestine when compared to perch captured 8 km away and in the reference areas. Autoradiograms indicated a diagonal zone consisting of multiple overlapping adducts, a pattern typical of exposure to a complex mixture of aromatic/hydrophobic genotoxic substances. No significant difference in adduct levels was detected between the years. Results from this study reveal that fish in the area closest to the mill are exposed to substances with a genotoxic potential.

Animals↗
PubMed2000

The endogenous adjuvant squalene can induce a chronic T-cell-mediated arthritis in rats.

Squalene is a cholesterol precursor, which stimulates the immune system nonspecifically. We demonstrate that one intradermal injection of this adjuvant lipid can induce joint-specific inflammation in arthritis-prone DA rats. Histopathological and immunohistochemical analyses revealed erosion of bone and cartilage, and that development of polyarthritis coincided with infiltration of alphabeta(+) T cells. Depletion of these cells with anti-alphabeta TcR monoclonal antibody (R73) resulted in complete recovery, whereas anti-CD8 and anti-gammadelta TcR injections were ineffective. The apparent dependence on CD4(+) T cells suggested a role for genes within the major histocompatibility complex (MHC), and this was concluded from comparative studies of MHC congenic rat strains, in which DA.1H rats were less susceptible than DA rats. Furthermore, LEW.1AV1 and PVG.1AV1 rats with MHC identical to DA rats were arthritis-resistant, demonstrating that non-MHC genes also determine susceptibility. Some of these genetic influences could be linked to previously described arthritis susceptibility loci in an F2 intercross between DA and LEW.1AV1 rats (ie, Cia3, Oia2 and Cia5). Interestingly, some F2 hybrid rats developed chronic arthritis, a phenotype not apparent in the parental inbred strains. Our demonstration that an autoadjuvant can trigger chronic, immune-mediated joint-specific inflammation may give clues to the pathogenesis of rheumatoid arthritis, and it raises new questions concerning the role of endogenous molecules with adjuvant properties in chronic inflammatory diseases.

Animals↗
PubMed2000

Effects of melagatran, an inhibitor of thrombin, on fibrin deposits, haemodynamics, and platelet count in endotoxaemic pigs.

BACKGROUND: Thrombin plays a pivotal role in the development of septic shock. Porcine endotoxaemia can replicate this condition. We wanted to evaluate whether melagatran, a novel inhibitor of thrombin, would counteract some of the endotoxin-induced changes in this model. METHODS: Fifteen pigs were anaesthetised, monitored (circulatory and respiratory variables) and subjected to an infusion of E. coli endotoxin at 10 microg x kg(-1) x h(-1). Six pigs were given melagatran during the first 3 h of the 6-h endotoxaemic period. Nine controls were given the corresponding volume of saline instead of melagatran. Specimens from the liver and the left lung were taken for light microscopy post mortem. RESULTS: The endotoxin-induced increase in pulmonary capillary wedge pressure and drop in platelet count were significantly less pronounced in the melagatran-treated pigs. Deposits of pulmonary fibrin were significantly reduced in the melagatran group, without improving oxygenation. Light microscopy revealed no hepatic fibrin in the pigs treated with melagatran in contrast to the endotoxaemic controls. Hepatic neutrophil accumulation was reduced in the melagatran group as compared to controls. Hepatocellular degeneration and plasma levels of tumour necrosis factor alpha (TNF alpha) and bilirubin were of the same magnitude in both groups. CONCLUSION: Melagatran reduced pulmonary capillary wedge pressure, a retrograde reflection of the left ventricular end-diastolic filling pressure, and also pulmonary stasis in pigs subjected to endotoxaemic challenge. Pulmonary and hepatic fibrin depositions were reduced, but PaO2 levels or liver function markers were not affected by melagatran during the early phase of endotoxaemia. Obstruction of the intrahepatic bile ducts, by fibrin depositions, is not responsible for reduced excretion of conjugated bilirubin during endotoxaemia. The beneficial effects of melagatran during endotoxaemia were not due to any reduction of plasma TNF alpha.

Animals↗
PubMed2000

Elastic pressure-volume curves indicate derecruitment after a single deep expiration in anaesthetised and muscle-relaxed healthy man.

BACKGROUND: In acute respiratory distress syndrome, lung volume is lost immediately after positive end-expiratory pressure (PEEP) is removed and is not immediately regained when PEEP is restored to its original value. The aim of this study was to investigate whether the same phenomenon also occurs in cardiopulmonary healthy individuals during anaesthesia and muscle relaxation. METHODS: In 13 anaesthetised and muscle-relaxed patients, inspiratory elastic pressure-volume (Pel-V) curves were, after lung recruitment, obtained from zero end-expiratory airway pressure (ZEEP) and from a PEEP of 5 cmH2O. The curves were aligned on a common volume axis. Differences in lung volumes and compliance (Crs) were calculated at the different airway pressures. RESULTS: At comparable pressures the ZEEP curve showed significantly lower volumes up to an airway pressure of 25 cmH2O. Maximum Crs was similar on the curves obtained from ZEEP and PEEP. However, the lower segments of the curve recorded from PEEP showed lower Crs compared to the curve recorded from ZEEP. CONCLUSION: During anaesthesia and muscle paralysis, the Pel-V relations change immediately when 5 cmH2O of PEEP is removed. This phenomenon is probably mainly caused by closure of small airways and only in a minor part, if any, by formation of atelectasis. This study indicates that under these conditions lung volume might easily be normalised by a large breath producing an airway pressure of 20 cmH2O.

Adult↗
PubMed2000

Solitary fibrous tumour of the oral cavity: clinicopathological and immunohistochemical characterization of three cases.

Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm rarely located in the oral cavity. To characterize further oral SFT, we describe three new cases. Each tumour originated in the buccal mucosa of a middle-aged/elderly patient. Histological examination showed well-circumscribed tumours with densely cellular areas alternating with hypocellular areas in a variedly collagenous, vascular stroma. Mast cells were abundant. The spindle-shaped, neoplastic cells immunostained strongly for CD34 antigen and vimentin and weakly for bcl-2, but not for epithelial cell markers, alpha-smooth muscle actin, or neurofilament or S-100 proteins. Compatible with the virtual absence of mitoses and of marked nuclear atypia, the overall frequency of proliferating cells expressing Ki-67 was low. The expression of CD34 was useful in the differential diagnosis. The consistent location in the cheek and expansion of one tumour after local trauma does not preclude a traumatic element in the development of oral SFT.

Aged↗
PubMed2000

Evaluation of endothelium-dependent vasodilation in the human peripheral circulation.

Flow-mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic-receptor agonist have both frequently been used to evaluate endothelium-dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor-agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L-arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion. While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated (r = 0.70, P < 0.01), FMD showed no relationship with the vasodilation evoked by MCh (r = -0.03) or L-arginine (r = 0.04). The five-fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations (P < 0.05) and a more than 11-fold increase in forearm NOx-release (P < 0.01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium-independent vasodilation evoked by NO-donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium-dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO-release.

Adult↗
PubMed2000

Intestinal mucosal secretion of basic fibroblast growth factor in patients with ulcerative colitis.

BACKGROUND: Basic fibroblast growth factor (bFGF) promotes angiogenesis and several other biologic processes, including proliferation of mesenchymal cells and tumor progression. We investigated whether bFGF could be detected in the intraluminal secretion of the small intestine, sigmoid colon, and rectum in healthy individuals and in patients with ulcerative colitis. METHODS: We used endoscopic perfusion techniques to obtain samples from well-defined intestinal segments. The perfusion fluid concentrations of bFGF, biochemical markers of inflammation, myeloperoxidase (MPO), interleukin-6 (IL-6), and permeability (albumin) were determined with immunochemical methods. RESULTS: In the perfusion fluids the albumin concentration, which reflects passive diffusion, was less than 1% of the plasma concentration, whereas the intestinal concentration of bFGF was similar to that in plasma. Among healthy subjects the concentration of bFGF was eightfold higher in the jejunum and twofold higher in the rectum than in the sigmoid colon. The perfusion fluid from colorectal segments in patients with ulcerative colitis had a significantly higher mean concentration of bFGF than that from healthy individuals; an almost 10-fold difference was found in rectal segments. There were strong correlations between the concentration of bFGF and the concentrations of MPO and IL-6. CONCLUSIONS: The high concentrations of bFGF in the intestinal perfusion fluid reflect either a local synthesis or an active secretion of bFGF within the mucosa. The bFGF concentration differs in intestinal anatomic location and increases significantly in patients with ulcerative colitis in close relationship with biochemical markers of inflammation and permeability.

Adult↗
PubMed2000

Quantitative bone scintigraphy. A methodological evaluation in prostate cancer.

PURPOSE: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). MATERIAL AND METHODS: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). RESULTS: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. CONCLUSION: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.

Aged↗
PubMed2000

Scalding injuries in immigrant families.

From 1990 to 1996, 214 patients aged up to 6 years were treated at our inpatient burns unit. Ages ranged from 3 to 70 months. Scalding was the cause in 186 cases. The median size of the burned areas was 5.0% (range 0.5%-40%). One hundred and nine were deep dermal burns that required surgical treatment, but this was refused in seven instances. Duration of hospital stay was 11 days (2-45). The number of follow-up visits ranged from 0 to 17. Secondary reconstructions for scarring have been done for seven children so far. Ninety-eight (46%) came from immigrant families, mostly from the Middle East and the Balkans. Of the 186 scalded children, 94 (51%) were immigrants, and they also had a tendency to have more severe injuries. Explanations might be that they were more likely to cook with water and oil, they were unfamiliar with Swedish safety standards and measures, and they had difficulty in communicating (language) and a limited social network. The ensuing scar also may disturb or delay the child's adaptation to the new environment. Our preventive work is now based on a model that states that frequency, type, and severity of injury is dictated by the variables: risk, personality, supervision, and education.

Burns↗