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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 73 records · Page 4Linked to original sources

Effects of lung recruitment maneuver and positive end-expiratory pressure on lung volume, respiratory mechanics and alveolar gas mixing in patients ventilated after cardiac surgery.

BACKGROUND: It is unclear whether positive end-expiratory pressure (PEEP) is needed to maintain the improved oxygenation and lung volume achieved after a lung recruitment maneuver in patients ventilated after cardiac surgery performed in the cardiopulmonary bypass (CPB). METHODS: A prospective, randomized, controlled study in a university hospital intensive care unit. Sixteen patients who had undergone cardiac surgery in CPB were studied during the recovery phase while still being mechanically ventilated with an inspired fraction of oxygen (FiO2) 1.0. Eight patients were randomized to lung recruitment (two 20-s inflations to 45 cmH2O), after which PEEP was set and kept for 2.5 h at 1 cmH2O above the pressure at the lower inflexion point (14+/-3 cmH2O, mean +/-SD) obtained from a static pressure-volume (PV) curve (PEEP group). The remaining eight patients were randomized to a recruitment maneuver only (ZEEP group). End-expiratory lung volume (EELV), series dead space, ventilation homogeneity, hemodynamics and PaO2 (oxygenation) were measured every 30 min during a 3-h period. PV curves were obtained at baseline, after 2.5 h, and in the PEEP group at 3 h. RESULTS: In the ZEEP group all measures were unchanged. In the PEEP group the EELV increased with 1220+/-254 ml (P<0.001) and PaO2 with 16+/-16 kPa (P<0.05) after lung recruitment. When PEEP was discontinued EELV decreased but PaO2 was maintained. The PV curve at 2.5 h coincided with the curve obtained at 3 h, and both curves were both steeper than and located above the baseline curve. CONCLUSIONS: Positive end-expiratory pressure is required after a lung recruitment maneuver in patients ventilated with high FiO2 after cardiac surgery to maintain lung volumes and the improved oxygenation.

Aged↗

Disease activity in rheumatoid arthritis: fibrinogen is superior to the erythrocyte sedimentation rate.

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the most widely used assays to measure the laboratory aspect of the acute-phase response, being of great value in monitoring disease activity in rheumatoid arthritis (RA). The ESR is influenced by several factors, and mainly by fibrinogen. Therefore the relationships between ESR, fibrinogen and CRP and their correlations with a patient questionnaire score on activities of daily living, the Modified Stanford Health Assessment Questionnaire (MHAQ) were studied. Fifty-four consecutive patients with RA admitted to the hospital were recruited to this cross-sectional study. Strong mutual correlations were found between the studied acute-phase markers (p<0.000000001). Fibrinogen and CRP rates showed highly significant correlations with MHAQ, whereas ESR did not. We suggest that ESR could be replaced by fibrinogen in the assessment of RA in order more accurately to assess the slower component of the acute-phase response and to have a variable that shows better correlation with disability.

Activities of Daily Living↗

Tumour markers as early predictors of response to chemotherapy in advanced colorectal carcinoma.

BACKGROUND: To evaluate the reliability and validity of serum carcinoembryonic antigen (CEA), tissue polypeptide-specific antigen (TPS), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in monitoring palliative chemotherapy in advanced colorectal cancer (ACRC). METHODS: Serum was prospectively collected from 87 patients with ACRC treated with first-line 5-fluorouracil and leucovorin before and 2, 4 and 10 weeks after induction. RESULTS: Eight patients had normal baseline TPS levels, and these patients had a favourable outcome with prolonged survival and a higher rate of objective responses than patients with elevated TPS levels. At 10 weeks, all responders had a decreasing TPS value. The sensitivity for a decrease of >25% using TPS was 83% and 86% for objective and subjective responses, respectively, and the specificity was 65% and 72%, respectively. CEA had, in the same setting, a sensitivity of 45% and 46%, respectively, and the specificity was 88%. VEGF was elevated in 54% of the patients and bFGF in 15% of the patients. The VEGF values decreased during therapy in 94% of the patients, but the changes in serial VEGF values did not correlate with survival or response. Tumour markers used together did not enhance the predictive values of TPS alone. CONCLUSIONS: Repeated measurements of CEA, VEGF and bFGF in serum are of limited value in monitoring chemotherapy in ACRC. TPS seems to be of greater interest, but does not predict exactly which patients are going to have a positive outcome of palliative chemotherapy.

Adenocarcinoma↗

Serum concentrations of cartilage oligomeric matrix protein, fibrinogen and hyaluronan distinguish inflammation and cartilage destruction in experimental arthritis in rats.

OBJECTIVES: We investigated if changes in serum/plasma fibrinogen (FIB), hyaluronan (HA) and cartilage oligomeric matrix protein (COMP) levels can be used to differentiate between inflammation and cartilage involvement during arthritis. METHODS: Collagen-induced arthritis (CIA), oil-induced arthritis (OIA) and for comparison, experimental autoimmune encephalitis (EAE) induced in DA rats were investigated. RESULTS: Elevations of FIB concentrations were apparent at days 4-7 post-immunization in both arthritis models reaching a maximum on day 20-21, i.e. before peak arthritis. Elevations of HA in both models were seen shortly before macroscopically apparent arthritis, and peaked at or just before maximal arthritis, i.e. later in CIA than in OIA. COMP levels increased only after onset of arthritis and peaked late in disease (days 34-37), being significantly higher in the more destructive CIA compared with the less destructive OIA. During EAE flares, only FIB levels increased. CONCLUSIONS: FIB is a general inflammation marker, HA appears to be a marker for synovitis and changes in COMP levels appear to reflect the cartilage destruction process.

Animals↗

Feline odontoclastic resorptive lesions: unveiling the early lesion.

The purpose of this study was to increase understanding of the factors initiating feline odontoclastic resorptive lesions (FORLs). Fifty-six teeth (clinically and radiographically unaffected by ORLs) were harvested. Of these, 43 were from cats that had ORLs in other teeth (group A) and 13 were from cats with no clinical or radiographic evidence of ORLs in any teeth (group B). Twenty-six teeth in group A and one tooth in group B showed histological evidence of external root resorption (surface resorption and replacement resorption resulting in ankylosis). Some teeth in group B showed healed cementum resorption. It has previously been assumed that FORLs were similar to lesions associated with peripheral inflammatory root resorption, and were associated with periodontal disease. These histological findings suggest instead that a FORL is a non-inflammatory replacement resorption, resulting in ankylosis. The periodontal ligament of resorbing teeth lacked normal fibrous architecture, but was not inflamed. Resorption was not identified in cervical cementum. However, the histological appearance of the cervical cementum differed between the two groups. Several aetiopathogenetic explanatory models which arise from these observations are discussed.

Animals↗

ADP activation induces bFGF binding to platelets in vitro.

Basic fibroblast growth factor (bFGF), is a heparin-binding factor with potent angiogenic properties in vitro and in vivo. bFGF is involved in tumour growth, but it has also been shown to reduce infarct size in experimentally induced acute myocardial infarction. Platelets are also believed to have an important role in both tumour growth and myocardial infarction. We have studied bFGF binding to platelets by flow cytometry. Platelet activation by ADP induces bFGF binding to platelets. bFGF bound to activated platelets will result in a locally high concentration of bFGF in patients with myocardial infarctions and malignant tumours. Addition of recombinant bFGF to platelet rich plasma reduced the percentage of fibrinogen positive platelets. bFGF may thus have an inhibitory effect on platelet aggregation.

Adenosine Diphosphate↗

Cooperative binding of gamma-glutamyl substrate to human glutathione synthetase.

Human glutathione synthetase is responsible for catalyzing the final step in glutathione biosynthesis. It is a homodimer with a monomer subunit MW of 52 kDa. Kinetic analysis reveals a departure from linearity of the Lineweaver-Burk double reciprocal plot for the binding of gamma-glutamyl substrate, indicating cooperative binding. The measured apparent K(m) values for gamma-glutamyl-alpha-aminobutyrate (an analog of gamma-glutamyl-alpha-aminobutyrate) are 63 and 164 microM, respectively. Neither ATP (K(m) of 248 microM) nor glycine (K(m) of 452 microM) exhibits such cooperative binding behavior. Although ATP is proposed to play a key role in the sequential binding of gamma-glutamyl substrate to the enzyme, the cooperative binding of the gamma-glutamyl substrate is not affected by alterations of ATP concentration. Quantitative analysis of the kinetic results for gamma-glutamyl substrate binding gives a Hill coefficient (h) of 0.75, indicating negative cooperativity. Our studies, for the first time, show that human glutathione synthetase is an allosteric enzyme with cooperative binding for gamma-glutamyl substrate.

Adenosine Triphosphate↗

Rats made congenic for Oia3 on chromosome 10 become susceptible to squalene-induced arthritis.

Several quantitative trait loci (QTLs) regulating the risk of experimental arthritis have been identified by genome-wide linkage analyses, but only the MHC has thus far been reported to transfer arthritis susceptibility in congenic animals. We have produced a congenic strain for Oia3, a genetic factor originally identified as an oil-induced arthritis (OIA) QTL in arthritis-prone DA rats. A 46 cM telomeric region of chromosome 10 encompassing Oia3 was transferred from DA rats to MHC-identical but minutely arthritis-susceptible LEW.1AV1 rats by selective breeding. Arthritis development was provoked in Oia3-congenic rats by intradermal injection of different adjuvant oils. One successful arthritis trigger was squalene, which is approved for vaccinations in humans and has been implicated in Gulf War syndrome. The endogenous cholesterol precursor squalene induced T cell infiltration into joints and macroscopic arthritis in Oia3-congenic rats and DA rats, whereas LEW.1AV1 rats were almost resistant. Arthritis onset, approximately 14 days post-injection, coincided with arrested body-weight gain and increased plasma levels of the inflammation markers fibrinogen and alpha 1-acid glycoprotein. Congenic rats displayed intermediate phenotypes compared with the two parental strains, and similar to rheumatoid arthritis in humans, female preponderance was observed in Oia3-congenic rats. Finally, recombinant rat strains were constructed and were used to map a susceptibility gene(s) in females to a telomeric 4--19 cM Oia3 subregion. The experimental system described allows transformation of multifactorial arthritis susceptibility into dichotomous phenotypes.

Animals↗

[A case report. Hypotensive reaction caused by albumin infusion].

Hypotensive reactions during surgical procedures cause diagnostic problems in establishing whether the hypotension is due to blood loss or pharmaceuticals or other causes. A case of hypotension probably due to an albumin infusion is described. Bradykinin effects are probably the cause of many hypotensive reactions. Angiotensin-converting enzyme (ACE) inhibitors reduce degradation of bradykinin and thus increase the risk of hypotensive reactions. When possible, doctors should consider withholding ACE inhibitors 24 hours before surgical procedures likely to require albumin transfusions.

Angiotensin-Converting Enzyme Inhibitors↗

Angiogenesis and angiogenic growth factors in Wilms tumor.

PURPOSE: Angiogenesis, that is new blood vessel formation, is a prerequisite for growth and metastasis of solid tumors. This study was undertaken to quantify tumor capillaries, investigate immunohistochemical expression and measure serum concentrations of angiogenic growth factors in patients with Wilms tumor. MATERIALS AND METHODS: The hospital records of 33 patients were reviewed and new slides were stained for the endothelial cell marker CD31. Capillaries were quantified in the most vascularized part of the tumor (hot spot) and in the whole slide. New slides were stained immunohistochemically for the angiogenic growth factors angiogenin, basic fibroblast growth factor (bFGF), transforming growth factor alpha, transforming growth factor beta1-3, tumor necrosis factor alpha and vascular endothelial growth factor (VEGF), and their immunoreactivity was quantified. Pretreatment serum samples from 14 patients and 56 healthy control children were analyzed using enzyme-linked immunosorbent assay kits for angiogenin, basic fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, tumor necrosis factor alpha and VEGF. RESULTS: Logistic regression analysis and Kaplan-Meier estimates showed that quantifications based on the tumor hot spot had a significant impact on survival probability (p <0.05). The tumor hot spot counts were highest in the blastemal compartment. Levels of hepatocyte growth factor and VEGF in serum were 3 times higher than those in controls (p <0.01). CONCLUSIONS: Although the sample size is small in this study, the results imply that angiogenesis in Wilms tumor is driven by angiogenic growth factors, and that intratumoral capillary quantification and determinations of serum levels of angiogenic growth factors may be of clinical value.

Child↗

Neonatal screening for metabolic, endocrine, infectious, and genetic disorders. Current and future directions.

There are good reasons to expect that future neonatal screening will expand both to include more disorders and to cover more of the global newborn population. Disorders for which neonatal screening will be given high priority in the health care field in the future are CH and PKU. Screening for CH is likely to expand faster than screening for PKU, especially in the developing world. In the future, screening for CAH will be practiced much more widely than today. Screening for CF is likely to qualify for routine neonatal screening in the future, especially if gene therapy becomes successful. Screening for infectious diseases is an area that is also developing rapidly. Which disorders to screen for neonatally will depend on a number of factors that are unique to each society, such as the prevalence, economy, and ethics. This must be realized when international guidelines are drafted. Technical development, which is of major importance for neonatal screening, includes MS-MS, different DNA techniques, and automation. The expansion of biomedical knowledge in a wide variety of fields will establish new grounds for neonatal screening.

Chromosome Disorders↗

Coagulation and complement activation.

UNLABELLED: The purpose of this investigation was to assess the effect of heparin coating of a new stent construction (Stent Graft, Jomed Implantate GmbH, Germany) on platelet and coagulation activity. METHODS: Stent grafts with an ePTFE membrane interfoliated between two stents were deployed in tubings to form Chandler loops. Fresh human blood with a low concentration of heparin was rotated for 1 h, then collected and used for measurements of platelet number, thrombin-antithrombin complex (TAT), CD11b, C3a and C5b-9. There were five study groups: Group 1, conventional unmodified stents (n = 8); Group 2, untreated stent grafts (n = 8); Group 3, heparin-coated stents and untreated membrane (n = 7); Group 4, heparin-coated stents and membrane (n = 8); Group 5, heparin-coated PVC tubings with no stents (n = 8). RESULTS: There was a significant drop in platelet count, increase in TAT-values and CD11b expression in Groups 1-3 but not in Group 4 compared to Group 5. Examination by scanning electron microscopy revealed extensive activation on non-modified stents but almost no deposition of thrombotic material on heparin-modified stent grafts. CONCLUSIONS: With unmodified stents and membrane there were signs of significant activation of platelets and coagulation. In contrast, the heparin-coated stent graft induced much less alterations, indicating improved blood compatibility.

Blood Coagulation↗

The pressure at the lower inflexion point has no relation to airway collapse in surfactant-treated premature lambs.

BACKGROUND: The lower inflexion point (LIP) on the inspiratory part of the pressure-volume (PV) loop has been suggested to be related to the pressure at which air spaces collapse. Our hypothesis is that airway collapse might instead be assessed from the upper inflexion point on the expiratory part of the PV-loop (UIPexp), where lung volume starts to decrease significantly. We therefore examined whether there was a relation between LIP and UIPexp in premature surfactant-treated lambs. METHODS: Ten lambs, at 119-141 days of gestational age, were delivered by cesarean section and given 200 mg/kg modified natural porcine surfactant before the first breath. The lambs were then connected to a ventilator and PV-loops using airway pressures of 0-35-0 (ZEEP-loop) and 5-35-5 cmH2O (PEEP-loop) were obtained after lung recruitment at 15, 60 and 120 min after birth. From the loops, LIP, UIPexp, upper inflexion point of the inspiratory part of the loop (UIP insp), inspiratory capacity (IC) as well as inspiratory and expiratory maximal compliance of the respiratory system (Crs(insp) and Crs(exp)) were calculated. RESULTS: The ZEEP-loop showed a substantial hysteresis with a distinct LIP at 19+/-2 cmH2O (mean+/-SD), which was different (P<0.001) from UIPexp (9+/-2 cmH2O). The pressures at LIP and UIPexp were unrelated (r2=0.06). UIPinsp was located at 28+/-2 cmH2O. Crs(insp) was 2.1+/-0.6 ml x cmH2O(-1) x kg(-1), which was lower (P<0.001) than Crs(exp) (2.8+/-0.6 ml x cmH2O(-1) x kg(-1)). IC was 26+/-6 ml/kg. The PEEP-loop had a minimal hysteresis with an expiratory part coinciding with that of the ZEEP-loop. CONCLUSION: In surfactant-treated premature lambs the pressures at LIP and UIPexp are not related, showing that LIP does not indicate the pressure at which airways collapse.

Anesthesia↗