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Biomedical subjects

T Andersson

Publications and source records attributed to T Andersson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Involvement of adenomatous polyposis coli (APC)/beta-catenin signalling in human breast cancer.

We studied the relevance of adenomatous polyposis coli (APC)/beta-catenin signalling in the development of breast cancer by analysing the expression of beta-catenin in 54 primary breast tumours (34 ductal and 20 lobular). We showed that 13% of the tumours exhibited upregulated levels of beta-catenin in the cytosol suggesting that defects in APC/beta-catenin signalling components had lowered the rate of beta-catenin degradation. No mutations were observed in the amino-terminal region of beta-catenin, which comprises conserved serine residues important for phosphorylation-dependent degradation of the protein, but the APC protein was altered in 6% of the tumours. Tyrosine phosphorylation of beta-catenin was detected in only one tumour and could, therefore, not have been responsible for the observed increased levels of this protein. Although 9% of the tumours displayed upregulation of c-MYC protein, there was no correlation with beta-catenin overexpression, suggesting that increased beta-catenin expression is not the major cause of c-myc gene activation in breast cancer. It is imperative that elements that selectively drive the oncogenic activity of beta-catenin in breast cancer be identified.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Nonpolar components of the latex of Euphorbia peplus.

The less polar fractions of the latex of Euphorbia peplus were found to contain obtusifoliol, cycloartenol, 24-methylenecycloartanol, lanosterol, and 24-methylenelanosterol in the free and esterified triterpene alcohol fractions; 9-cis-tricosene as the major component of the hydrocarbon fraction; and a new acyclic triterpene alcohol named peplusol (1). The structure of 1 was determined as the R-isomer of (all-E)-2-(5,9-dimethyl-1-methylene-4,8-decadienyl)-5,9, 13-trimethyl-4,8,12-tetradecatrien-1-ol by spectral and chemical methods.

Alcohols↗
PubMed2000

Associations between different aspects of alcohol habits in adolescence, early adulthood, and early middle age: a prospective longitudinal study of a representative cohort of men and women.

Previous research has indicated that the relation between adolescent and adult alcohol habits is not very strong. The objective of the present study was to illustrate associations between different aspects of alcohol habits from adolescence to early middle age in a normal, representative Swedish birth cohort of male (n = 122) and female (n = 90) participants. The sample was prospectively followed by means of self-reports on drinking habits at ages 18, 25, and 36. The results show that heavy drinking at age 18 and frequent intoxication at age 25 substantially increase the risk of heavy consumption at age 36 but that hazardous alcohol habits at either age 18 or 25 alone cannot be considered a substantial risk factor.

Adolescent↗
PubMed2000

Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid-related diseases. METHODS: In this double-blind crossover study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic variables were measured. RESULTS: Thirty-six patients aged 29-58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS: Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.

Adult↗
PubMed2000

Effect of cooling suit treatment in patients with multiple sclerosis evaluated by evoked potentials.

The aim of the present study was to determine whether any significant alterations of evoked potentials could be detected after treatment of patients with multiple sclerosis with a cooling suit. All patients had previously experienced a positive effect of this treatment. Six patients were investigated with visual, sensory and motor evoked potentials and six further patients with only motor evoked potentials. All patients had relevant clinical lesions. The mean values for the group of patients were similar before and after cooling, but a few individuals showed a substantial improvement of motor evoked potentials after cooling, with increased amplitude and/or shortened central motor conduction time. There was also a weak, but significant, correlation between temperature decrements and the reduction of central motor conduction time. However, since the central motor conduction times of most patients were only slightly affected, this effect could explain only a small part of the beneficial effect of cooling. Effects on cognition and executive ability or improvement of spasticity may be of greater importance.

Adult↗
PubMed2000

Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.

Administration, Oral↗
PubMed2000

Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study.

An impaired fibrinolytic function due to elevated plasma levels of plasminogen activator inhibitor (PAI)-1 activity or tissue plasminogen activator (tPA) antigen is correlated with the development of myocardial infarction (MI) in patients with manifest coronary heart disease. Recently, methods for determining the specific tPA/inhibitor complexes constituting tPA antigen in plasma have become available. In the Stockholm Heart Epidemiology Program (SHEEP) study, 86 of 1212 MI patients, subjected to blood sampling in a metabolically stable period, suffered reinfarction before the end of 1996. These individuals have been compared with an approximately equal number of matched MI patients without recurrence and a group of matched healthy control subjects regarding the plasma concentrations of some hemostatic factors. The hemostatic compounds studied (fibrinogen, von Willebrand factor, tPA antigen, PAI-1, and the tPA/PAI-1 complex) were typically higher in the groups (men and women) with recurrence of MI compared with those without. The plasma concentrations were also typically higher in the pooled groups of patients compared with the groups of healthy control subjects. The largest between-group differences were found for the plasma tPA/PAI-1 complex. The crude odds ratio for reinfarction associated with higher concentration (>/=75th percentile among the control subjects) of tPA/PAI-1 was 1.8 (95% CI 1.1 to 3.1); the corresponding crude odds ratio for von Willebrand factor was 2.3 (1. 3 to 4.0). The tPA/PAI-1 complex correlated strongly with PAI-1 and tPA antigen in all groups and with serum triglycerides and body mass index in all groups except for women with reinfarction. An increased plasma level of tPA/PAI-1 complex is a novel risk marker for recurrent MI in men and women. Most likely, increased plasma levels of tPA/PAI-1 complex reflect impaired fibrinolysis, because the correlation with PAI-1 is strong. Further support is obtained indicating that the plasma concentration of von Willebrand factor is also an important risk marker for recurrent MI.

Aged↗
PubMed2000

Community-based prevention of perinatal deaths: lessons from nineteenth-century Sweden.

BACKGROUND: Perinatal deaths have been more difficult to prevent than infant deaths in low- income countries due to its close relation to poor maternal outcome. The aim of the study was to perform a comprehensive population-based analysis of perinatal mortality in a high mortality setting and to determine the impact of midwifery-assisted home deliveries. METHOD: The study design was a community-based cohort study. In all, 4876 perinatal deaths were recorded among 116 211 newborns in the districts of Sundsvall and Skellefteâ in northern Sweden during the years 1831-1899. Relative risks, 95% CI, population attributable proportions and prevented fractions were calculated. RESULTS: The overall perinatal mortality rate was 42.0 per 1000 births. A previous stillbirth represented one of the most important risk factors (RR = 3.25, 95% CI : 2.97-3.56), with a population attributable proportion of 7%. Two or more previous stillbirths gave an RR of 8.50 (95% CI : 7.58-9.53) and a population attributable proportion of 4%. There was an increased risk of perinatal mortality for mothers over 35 years old, the primiparous and the unmarried, while grandparous women had a higher perinatal mortality that was accounted for completely by a poor history of previous stillbirths and infant deaths among these women. The children of crofters, farmers and workers had higher perinatal mortality, but area had no significant impact. During the years 1881-1890 and 1891-1899, the prevented fractions of midwifery were 15% and 32%, respectively. CONCLUSION: Poor reproductive history, particularly previously high perinatal mortality, is associated with high perinatal mortality. Midwifery-assisted at home deliveries successfully reduced perinatal mortality.

Female↗
PubMed2000

Swedish maternal mortality in the 19th century by different definitions: previous stillbirths but not multiparity risk factor for maternal death.

BACKGROUND: The high maternal mortality levels in today's developing countries were also found throughout the history of currently affluent countries. The parish information system in Sweden offers unique possibilities for research in historical cohorts. Furthermore, vital events surveillance systems are scarce in today's developing countries. METHODS: This cohort study covers 42,387 mothers who gave birth to 150,932 infants during the 19th century in the Skellefteå and Sundsvall areas. Among these women, 1,237 were dead within one year after delivery. The analysis of the cause of these deaths was done according to the various ICD definitions. Parity five and above was defined as grand multiparity. RESULTS: Maternal mortality ratios, deaths per 100,000 live births were as follows: 256.4 (direct obstetric deaths), 320.7 (direct and indirect obstetric deaths), 489.2 (pregnancy-related deaths), 347.8 (late maternal deaths) and 837.0 (maternal deaths and late maternal deaths). In this study, 59% of all maternal deaths occur within the first 42 days of delivery, two thirds of them having direct and indirect obstetric causes. Of the late maternal deaths, the bulk were infectious or other indirect deaths, mirroring more general female mortality and the pre-existent endemic situation of tuberculosis and other infectious diseases. The combination of previous stillbirth and infant death represented the highest risk ratios, RR 2.77-3.62, while grand multiparity was not associated with increased risk. Urbanized and industrialized areas tended to have higher maternal mortality. CONCLUSIONS: In conclusion, this study shows that the mother's reproductive history was the most important risk factor measured for all definitions of maternal death. Grand multiparity did not increase the risk of maternal death. Maternal mortality ratio varied threefold in the study population, depending on the definition used. The high mortality ratios found in this study, only declining by the end of the century, should be interpreted as a general condition of the society since no significant differences could be perceived regarding social class, while unmarried women were more at risk.

Cause of Death↗
PubMed2000

Aims, options and outcomes in measuring maternal mortality in developing societies.

BACKGROUND: Effective methods for measuring maternal mortality in developing countries are important, particularly in assessing interventions aiming for safer motherhood. Here the performance of different approaches is compared in the same setting. METHODS: Estimates of maternal mortality in a rural Ethiopian community are reported, made by direct observation, a case-control approach, and the sisterhood method. RESULTS: Adjusted estimates of MMR using these methods ranged between 440 and 665 per 100,000 live births. CONCLUSIONS: The advantages and disadvantages of the different approaches are compared, both for operational feasibility and outcome.

Adolescent↗
PubMed2000

Alcohol habits in a suburban male cohort.

OBJECTIVE: Using data from a prospective birth-to-maturity project, the study presents normally occurring variations in alcohol involvement of alcohol-related problems among a representative cohort of Swedish males in young middle age, born in a Swedish metropolitan area (n = 106). METHODS: Description and classification were based on an analysis of self-reported information (collected at about 36 years of age) about frequency and quantity of alcohol consumption (four-week timeline), self-reported alcohol-related symptoms, and registry data. RESULTS: According to a broad, operationally defined classification of "harmful drinking" (at least three alcohol-related symptoms, including alcohol-related crimes), 43 subjects (41%) had experienced a substantial drinking problem during their lifetime, to an extent that might warrant labels such as "alcoholism" or "hazardous drinking". About one-third of these misusers were currently using other drugs. Of the 106 subjects, 80 (75%) reported having had at least one alcohol-related symptom or problem at some time during their life. Taking various life events into account, including sociomedical circumstances and heavy consumption at 18 and 25 years, 23 subjects (22%) were classified as having a lifetime prevalence of alcohol abuse/dependence according to DSM-III criteria. CONCLUSION: Problem drinking was largely unknown to the healthcare system and only a few subjects had received treatment. The results are discussed in the light of data from other national and international epidemiological surveys.

Adult↗
PubMed2000

Variations and stability in drinking patterns in a cohort of Swedish males.

OBJECTIVE: Information on drinking patterns may make an important contribution to our understanding of the risks and consequences of alcohol consumption. The objective of the present study is to describe variations and stability of patterns of alcohol use at both the aggregate and the individual levels. METHODS: The reported alcohol consumption was recorded of a normal, representative birth cohort of Swedish male (n = 122) subjects followed from the age of 18 years to early middle age and more extensively scrutinized at the age of 36, using a 28 day time-line follow-back technique. RESULTS: In young middle age a high proportion of total consumption occurred on Fridays and Saturdays (about 60%). In addition, it was possible to classify "standard drinkers", "sporadic binge drinkers", and "frequent drinkers" as separate clusters. CONCLUSION: While binge drinking was more stable than frequency of drinking from the age of 18 to the age of 36, frequent drinking showed the highest short-term stability at the age of 36 years.

Adolescent↗
PubMed1999

Disruption of beta(2)-integrin-cytoskeleton coupling abolishes the signaling capacity of these integrins on granulocytes.

Integrin-dependent adhesion and dynamic modulations of the actin network are prerequisites for normal cell locomotion. To investigate whether the actin microfilamentous system does play a role in regulation of beta(2)-integrin-induced signalling, we pretreated granulocytes with staurosporine, a well-known protein kinase inhibitor that has also been shown to disrupt the cytoskeleton of intact cells. Pretreatment with staurosporine completely inhibited the beta(2)-integrin-induced Ca(2+) signal and also its ability to trigger actin polymerisation. This inhibition was not related to phosphorylation of the CD18-chain of the beta(2)-integrin, nor to inhibition of protein kinases. Instead, association of beta(2)-integrins with the cortical cytoskeleton, which was observed in untreated cells, was abolished after exposure to staurosporine, indicating that beta(2)-integrin signalling depends on integrin-cytoskeleton interaction. These results suggest not only that the actin network provides an adhesive link to the extracellular matrix and a driving force for the locomotory response, but also that it participates in regulation of beta(2)-integrin signalling during granulocyte locomotion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Temporal expression of a V(H) promoter-Cmu transgene linked to the IgH HS1,2 enhancer.

Immunoglobulin heavy chain (IgH) gene expression is guided by cis-regulatory elements which direct correct temporal and spatial expression in B lineage cells. One of these cis-acting elements is the IgH HS1,2 enhancer and previous studies in transgenic mice have revealed a temporally restricted activity of an HS1,2 enhancer-linked human beta-globin reporter gene in B lineage cells. To assess whether this enhancer can impose strict temporal regulation onto a V(H)-promoter-Cmu reporter gene, transgenic mice were generated. These mice expressed high serum levels of protein from the transgene. Moreover, high levels of transgene expression were observed in spleen and thymus, while lower expression was found in heart and kidney and no expression was detected in liver and brain. Interestingly, transgene expression was confined to large, activated B cells and peritoneal B cells but not observed in small, resting splenic B cells or activated T cells. However, upon mitogenic stimulation of resting B cells with LPS, high levels of transgene expression was induced. Our data demonstrate that the HS1,2 enhancer can interact with a natural V(H) promoter in a strict temporal fashion and when provided with an appropriate activation signal, this V(H) promoter/enhancer construct can induce transgene expression in resting B, but not T lineage cells. Our data are compatible with a model whereby the regulation of IgH gene expression may be subject to regulation by distinct subsets of cis-regulatory elements acting at different stages of B lymphocyte development. Thus, Ig gene expression may be regulated via an interaction between the V(H) promoter and 3' enhancer elements (here typified by the HS1,2 enhancer) in terminally differentiated B lineage cells.

Animals↗
PubMed1999

Sleep quality, carbon dioxide responsiveness and hypoxaemic patterns in nocturnal hypoxaemia due to chronic obstructive pulmonary disease (COPD) without daytime hypoxaemia.

In order to clarify whether nocturnal hypoxaemia (arterial oxygen saturation, SaO2 < 90%) may exist in the long-term before daytime hypoxaemia (PaO2 < 8.0 kPa) occurs in chronic obstructive pulmonary disease (COPD), 21 patients with stable severe COPD without daytime hypoxaemia (PaO2 > or = 8.0 kPa) were studied prospectively. Subjects were monitored twice by polysomnography (PSG) 12 months apart. Spirometry was performed, and diffusion capacity (DLCO) and hypercapnic respiratory drive response delta PI0.1 delta PCO2(-1)) were measured during the daytime in conjunction with polysomnography. At the start of the study our subjects had FEV1 %P (FEV1 as a percentage of predicted value) of 26.1 +/- 7.2%, a mean nocturnal nadir SaO2 of 83 +/- 5%, and a mean SaO2 during nocturnal hypoxaemic episodes of 88.0 +/- 0.7%. The patients' delta PI0.1 delta PCO2(-1) was 1.8 +/- 1.4 cm H2O kPa-1 (within the normal range). For the entire study group, no significant change in any lung function or blood gas parameter was noted during the year of observation, and nocturnal SaO2 remained unaltered. Stage I sleep decreased (P < 0.05) after 12 months. Prolonged stage I sleep was associated with nocturnal hypoxaemia at the second PSG. Five subjects developed daytime hypoxaemia and they showed poorer lung function but similar nocturnal hypoxaemia and delta PI0.1 delta PCO2(-1) level compared to the rest of the patients. Patients with sudden SaO2 dips had more pronounced nocturnal hypoxaemia and prolonged wakefulness than 'non-dippers'. In conclusion, the mean level of nocturnal hypoxaemia may persist unaltered for at least 1 yr. COPD patients with exclusively nocturnal hypoxaemia have a hypercapnic drive response within the normal range. Prolonged nocturnal hypoxaemia and reduced whole night oxygenation are associated with increased superficial sleep. Sleep fragmentation and high carbon dioxide sensitivity may be important defence mechanisms against sleep-related hypoxaemia. The appearance of daytime hypoxaemia is preceded by a substantial deterioration in lung function, but by only a minor deterioration of nocturnal hypoxaemia.

Aged↗
PubMed1999

PUVA and cancer risk: the Swedish follow-up study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Adolescent↗
PubMed1999

In vivo testing of the protection of gloves against acrylates in dentin-bonding systems on patients with known contact allergy to acrylates.

Occupational contact allergies to dental acrylates are increasing. Commonly used gloves protect poorly against acrylates. The protective efficacy in vivo of other, newer glove materials is not fully known. In this study, an open chamber system was used for testing the protection in vivo of 6 different gloves (1 vinyl glove, 2 latex gloves, 2 nitrile gloves and the 4H glove) against a commonly used dental adhesive, Scotchbond 1, containing 2-hydroxyethyl methacrylate (2-HEMA) and triethylene glycol dimethacrylate (TREGDMA). 8 patients with known contact allergy to 2-HEMA participated. Provocation with 50 microl of the adhesive for 7.5, 15 and 30 min was performed for each glove. The test demonstrated clear differences in the protective efficacy between the gloves. The 4H glove gave by far the best protection, followed by one of the nitrile gloves. One of the latex gloves and the vinyl glove gave a very poor protection against the adhesive. A dose-response relationship was observed between different application times of the acrylate product. The test model promises to be a useful clinical complement to in vitro methods in individual preventive measures against contact sensitization to acrylates.

Adhesives↗