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Biomedical subjects

E Pettersson

Publications and source records attributed to E Pettersson.

At least 19 recordsLinked to original sources
PubMed2005

Nuclear magnetic resonance and small-angle neutron scattering studies of anionic surfactants with macrocounterions: tetramethylammonium dodecyl sulfate.

Micellar solutions of tetramethylammonium dodecyl sulfate have been studied to determine the degree of counterion binding. Tetramethylammonium chloride was added over a wide range of surfactant concentrations such that the total concentration of tetramethylammonium ions in solution remained constant. Small angle neutron scattering experiments showed a constancy in aggregation number across this series, consistent with the constant C(aq) concept of Bales et al. (J. Phys. Chem. B 2001, 105, 6798). Pulsed-field gradient and electrophoretic NMR experiments were used to determine the degree of counterion dissociation, alpha, which was found to be 0.33. This value is in contrast to the value from conductivity measurements (alpha = 0.2), but supports the concept of an aggregation number based definition of alpha.

Magnetic Resonance Spectroscopy↗
PubMed2003

Causes and consequences of proteinuria: the kidney filtration barrier and progressive renal failure.

The past few years have witnessed a major breakthrough in the understanding of the molecular mechanisms and ultrastructural changes behind the development of proteinuria. The discovery of several proteins in the glomerular podocyte and slit diaphragm, where mutations lead to disease, has revealed the importance of this cell with its diaphragm as the major filtration barrier as opposed to the glomerular basement membrane (GBM) previously ascribed this function. Furthermore, accumulating clinical as well as experimental evidence points to the harmful effects of proteinuria, irrespective of the original damage. The purpose of this review is to shed light on what we know today about the two sides of this 'coin', the causes and the consequences of proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Adenovirus-mediated transfer of type IV collagen alpha5 chain cDNA into swine kidney in vivo: deposition of the protein into the glomerular basement membrane.

Gene therapy of Alport syndrome (hereditary nephritis) aims at the transfer of a corrected type IV collagen alpha chain gene into renal glomerular cells responsible for production of the glomerular basement membrane (GBM). A GBM network composed of type IV collagen molecules is abnormal in Alport syndrome which leads progressively to kidney failure. The most common X-linked form of the disease is caused by mutations in the gene for the alpha5(IV) chain, the alpha5 chain of type IV collagen. Full-length human alpha5(IV) cDNA was expressed in HT1080 cells with an adenovirus vector, and the recombinant alpha5(IV) chain was shown to assemble into heterotrimers consisting of alpha3(IV) and alpha4(IV) chains, utilizing a FLAG epitope in the recombinant alpha5(IV) chain. The results indicate that correction of the molecular defect in Alport syndrome is possible. Previously, we had developed an organ perfusion method for effective in vivo gene transfer into glomerular cells. In vivo perfusion of pig kidneys with the recombinant adenovirus resulted in expression of the alpha5(IV) chain in kidney glomeruli as shown by in situ hybridization and its deposition into the GBM was shown by immunohistochemistry. The results strongly suggest future possibilities for gene therapy of Alport syndrome.

Adenoviridae↗
PubMed2001

A 7-month outbreak of relapsing postpartum group A streptococcal infections linked to a nurse with atopic dermatitis.

A 7-month outbreak of 15 cases of postpartum sepsis with group A haemolytic Streptococci (GAS) was stopped when a carrier was identified. Comparing delivery dates with duty rotas revealed that the carrier had been present during delivery in 13 of the 15 cases. The epidemic GAS type, T3-13-B3264, was found in a carbuncle in her groin and in atopic dermatitis lesions behind her ears and on her eyelids. Thus, it was not the microbiological screening of staff that helped detect the carrier. The outbreak went unnoticed for 6 months, as no 2 cases were diagnosed by the same physician and 5 cases were diagnosed by different general practitioners. The main risk factors for infection were presence of the carrier relative risk (relative risk RR 47.8, 95% confidence interval (CI) 10.9-209.5) and suturing of episiotomy (RR 11.0; 95% CI 2.6-47.9). We recommend that a thorough epidemiological investigation should be carried out in every single case of GAS postpartum infection. Despite initial intravenous treatment with penicillin, 8 patients experienced > 15 recurring postpartum GAS infections, such as endometritis, wound infection, tonsillitis, erysipelas and Brodie's abscess. Eradication of GAS should be confirmed after completion of treatment.

Adult↗
PubMed2001

Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease.

BACKGROUND: Steroid dependent patients with Crohn's disease are at high risk of developing glucocorticosteroid induced side effects. AIMS: We evaluated the possibility of switching from systemic steroids to budesonide (Entocort) in prednisolone/prednisone dependent patients with inactive Crohn's disease affecting the ileum and/or ascending colon. PATIENTS: Steroid dependent patients with a Crohn's disease activity index </=200 were included. METHODS: In a double blind multicentre trial, 120 patients were randomly assigned to receive budesonide 6 mg once daily or placebo. Prednisolone was tapered to zero during the first 4-10 weeks and budesonide or placebo was given concomitantly and for a further 12 weeks. Relapse was defined as an index >200 and an increase of 60 points from baseline or withdrawal due to disease deterioration. RESULTS: After one and 13 weeks without prednisolone, relapse rates were 17% and 32%, respectively, in the budesonide group, and 41% and 65% in the placebo group (95% confidence intervals for the difference in percentages -41%, -8% and -51%, -16%; p=0.004 and p<0.001, respectively). The number of glucocorticosteroid side effects was reduced by 50% by switching from prednisolone and was similar in the budesonide and placebo groups. Basal plasma cortisol increased in both groups. CONCLUSIONS: The majority of patients with steroid dependent ileocaecal Crohn's disease may be switched to budesonide controlled ileal release capsules 6 mg without relapse, resulting in a sharp decrease in glucocorticosteroid side effects similar to placebo, and with an increase in plasma cortisol levels.

Adolescent↗
PubMed2000

Onset of action of intranasal budesonide (Rhinocort aqua) in seasonal allergic rhinitis studied in a controlled exposure model.

BACKGROUND: Intranasal budesonide aqueous nasal spray (BANS) is recognized as an efficacious treatment for seasonal allergic rhinitis (SAR), but the time to onset of action is not known. OBJECTIVE: The primary objective was to evaluate the time at which the onset of action of BANS in the symptomatic relief of seasonal allergic rhinitis becomes evident within 12 hours after a single dose in a controlled ragweed pollen exposure setting. METHODS: The study was of a double-blind, randomized, parallel-group design, testing BANS (64 microgram and 256 microgram) and placebo on ragweed-sensitive subjects with symptoms for at least 1 year by using a controlled pollen challenge system (Environmental Exposure Unit). The efficacy variables were the combined nasal score (the sum of blocked nose, runny nose, and sneezing-itchy nose), individual nasal symptoms, overall evaluation of treatment efficacy reported by participants on diaries, and peak nasal inspiratory flow (PNIF). RESULTS: A total of 217 participants were treated with BANS or placebo. At 7 to 12 hours, BANS was better than placebo in reducing combined nasal and blocked nose symptoms. For PNIF, the time to onset of action was shortest for 256 microgram of BANS relative to placebo (3 hours, P =.003). BANS 64 microgram was better than placebo in reducing the individual scores of blocked nose, runny nose, and sneezing-itchy nose from 3 to 5 hours after administration. Treatment efficacy was higher for those receiving BANS compared with placebo starting at 5 hours. All treatments were well tolerated, and no specific adverse events occurred. CONCLUSIONS: The onset of action of intranasal BANS was 7 hours according to combined nasal and blocked nose symptom scores. Evidence of earlier response was observed at 3 hours for runny nose and PNIF.

Administration, Intranasal↗
PubMed2000

T cell activation in patients with ANCA-associated vasculitis: inefficient immune suppression by therapy.

BACKGROUND AND AIMS: Patients with vasculitic disease and autoantibodies to neutrophil cytoplasmic antigens (ANCA) generally respond to immunosuppressive therapy with a reduction of the inflammation and lowering of the ANCA titre. However, most patients experience relapses, sometimes after years of quiescence. In the present study we addressed the question whether the relapsing nature of this disease could be dependent on an underlying T cell activation. Patients were analyzed at disease onset, in remission while on treatment, and in quiescence. PATIENTS AND METHODS: Blood lymphocyte subsets and the expression of molecules associated with T cell activation were analyzed by flow cytometry and soluble interleukin-2 receptor (sIL2r) levels in serum by ELISA. Three patient categories (la, 1b and 2) were studied and compared with age-matched healthy controls (1a: 16 patients at onset of the disease before therapy, 1b: 10 patients from group 1a, re-analyzed after first remission, 2: 11 other patients in quiescence, 2-10 years after debut). RESULTS: All patient groups, 1a, 1b and 2, showed signs of T cell activation such as reduced CD28 on CD3+ and increased of the early T cell activation marker CD69 on CD3+, as well as of CD38 on CD8+ T cells. The sIL2r levels were significantly raised in all patient categories (la: 4280, 1b: 1844, 2: 2882 ng/ml) compared with the controls (923 ng/ml). CONCLUSION: Patients with ANCA-positive vasculitis show an increased expression of T cell activation markers irrespective of immunosuppressive therapy or disease phase. Such memory cells may form the basis for the remitting course of vasculitides and would be a rational target for new strategies of therapy.

Adult↗
PubMed1999

Evaluation of a nurse-run asthma school.

Important aims of the study were to investigate whether an educational program (the 'Asthma School') directed by a nurse led to improved knowledge of the disease, to improved self-medication and self-management and to improved, self-rated, functional status. A total of 32 patients (6 males, 26 females, mean age 43 years) was included. The following methods were used to collect the data before and one year after the Asthma School was completed; two study-specific questionnaires for collecting demographic data and measuring different aspects of the patients' knowledge of the disease and its treatment, monthly diary cards, lung-function tests (FEV1) and the Sickness Impact Profile (SIP) questionnaire. The main results of the study were an improved knowledge of the disease and its treatment, better self-management, i.e. more frequent use of the peak expiratory flow meter (PEF-meter) and use of inhaled bronchodilators on an as-required basis, fewer patients on sick-leave and a better, self-rated, physical health status. However, in spite of these encouraging results, the lungfunction was found to be unaffected, no pronounced changes in the use of asthma drugs could be found and the patients' need for medical care remained the same.

Adolescent↗
PubMed1999

CP/MAS 13C-NMR spectroscopy applied to structure and interaction studies on cellulose I.

Solid-state Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance (CP/MAS 13C-NMR) has been used to investigate the structure and interactions of cellulose I. The use of spectral fitting for the extraction of information from CP/MAS 13C-NMR spectra is reviewed and results obtained are discussed. Examples are shown where the method has been used to monitor the structural changes occurring in wood cellulose during kraft pulping. The effects observed on the cellulose and hemicelluloses are further investigated using a model system. Assignments of signal intensities originating from xylan-cellulose interactions are made.

Carbon Isotopes↗
PubMed1998

A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group.

BACKGROUND: Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both. METHODS: In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02). CONCLUSIONS: In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.

Administration, Topical↗
PubMed1998

Does the switch from sandimmun to Sandimmun neoral reduce patient need for Phenihydine?

In patients receiving cyclosporine A (CyA)-based immunosuppressive therapy, Ca2+ channel blockers (CCBs) prevent the development of CyA-related nephrotoxicity in which increased Ca2+ content plays an important role. We evaluated the dynamics of the intracellular (erythrocytes) and extracellular (plasma) Ca2+ levels and the influence of the CCB, Phenihydine, on this process during the conversion from Sandimmun (S) to Sandimmun Neoral (SN). Forty-two patients were enrolled. The conversion from S to SN normalized the elevated CA2+ level of erythrocytes in groups with Phenihydine (n = 20) and without Phenyhidine (n = 12) 4 weeks after the switch (P < 0.05); this level remained stable until the end of study. Therefore we suggest that the switch from S to SN is effective in reducing elevated intracellular Ca2+ levels. The decrease of Ca2+ content in erythrocytes was similar in all groups switched to SN (with or without Phenihydine). The last effect should be an important argument to focus the further long-term investigations on the ability of CCBs to act as cytoprotective and neophroprotective agents during immunosuppressive protocols with the new microemulsion formulation of CyA.

Adult↗
PubMed1998

High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.

Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.

Amino Acid Substitution↗
PubMed1997

Interaction of the novel antipsychotic drug amperozide and its metabolite FG5620 with central nervous system receptors and monoamine uptake sites: relation to behavioral and clinical effects.

Behavioral, biochemical, and electrophysiological studies suggest that amperozide affects mesolimbic and mesocortical dopamine neurotransmission. The receptor binding profile of amperozide is discussed and related to behavioral and clinical, i.e., antipsychotic, effects of the drug. As previously reported, amperozide displayed high affinity for serotonin 5-HT2A receptors (Ki = 16 nmol/L), and moderate affinity for striatal dopamine D2 (Ki = 540 nmol/L) and cortical alpha 1-adrenergic receptors (Ki = 172 nmol/L). In the present study amperozide displayed low affinity for several serotonin receptor subtypes as well as for the dopamine D4 receptor transfected in COS7 cells (Ki D4.2 = 769 nmol/L and Ki D4.4 = 384 nmol/L). Amperozide was very weak or did not interact with several other receptor species including adrenergic, histaminergic, muscarinic, benzodiazepine, gamma-aminobutyric acid, amino acid, opiate, and Ca channels; however, amperozide was found to compete for [3H]paroxetine binding for the serotonin transporter in the nanomolar range (Ki = 49 nmol/L). In vitro and in vivo binding potency of amperozide correlates best with behavioral effects, indicating 5-HT2A antagonism, although serotonin uptake inhibition may contribute to the effects of amperozide on dopamine neurotransmission. The metabolite of amperozide, FG5620, displayed 5-10 times lower pharmacologic activity than amperozide. These properties of amperozide may suggest that the antipsychotic effects of amperozide are mediated by 5-HT2A receptors, although 5-HT uptake inhibition and alpha 1-adrenergic receptor-mediated effects may be considered, particularly at higher doses.

Animals↗
PubMed1997

Metal ion interaction with cosubstrate in self-splicing of group I introns.

The catalytic mechanism for self-splicing of the group I intron in the pre-mRNA from the nrdB gene in bacteriophage T4 has been investigated using 2'-amino- 2'-deoxyguanosine or guanosine as cosubstrates in the presence of Mg2+, Mn2+and Zn2+. The results show that a divalent metal ion interacts with the cosubstrate and thereby influences the efficiency of catalysis in the first step of splicing. This suggests the existence of a metal ion that catalyses the nucleophilic attack of the cosubstrate. Of particular significance is that the transesterification reactions of the first step of splicing with 2'-amino-2'-deoxyguanosine as cosubstrate are more efficient in mixtures containing either Mn2+or Zn2+together with Mg2+than with only magnesium ions present. The experiments in metal ion mixtures show that two (or more) metal ions are crucial for the self-splicing of group I introns and suggest the possibility that more than one of these have a direct catalytic role. A working model for a two-metal-ion mechanism in the transesterification steps is suggested.

Bacteriophage T4↗