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M Eriksson

Publications and source records attributed to M Eriksson.

At least 73 records · Page 4Linked to original sources

Hypocalcemia during porcine endotoxemic shock: effects of calcium administration.

OBJECTIVE: To evaluate the pathophysiology involved in hypocalcemia in septic shock and to investigate the value of calcium administration. DESIGN: Prospective, randomized placebo-controlled trial with parallel groups. SETTING: Animal research laboratory at the University Hospital of Uppsala. SUBJECTS: Twenty-four pigs aged 12-14 wks receiving general anesthesia. INTERVENTIONS: Twenty pigs received endotoxin infusion (10 microg/kg/hr) for 6 hrs. Ten of these pigs also received a calcium infusion (20 mmol total) in parallel. Four control pigs received only saline. MEASUREMENTS AND MAIN RESULTS: At the end of the study, blood ionized calcium (Ca2+) had declined from 1.32+/-0.04 mmol/L (mean +/- SD) to 1.09+/-0.06 mmol/L in pigs receiving endotoxin (p < .05 vs. controls) compared with 1.38+/-0.04 mmol/L to 1.25+/-0.07 mmol/L in controls and 1.39+/-0.03 mmol/L to 1.24+/-0.07 mmol/L in endotoxemic pigs receiving calcium. In both endotoxemic groups, total calcium levels in ascites were increased by 56% (p < .005 vs. controls), and an accumulation of calcium in the liver was mainly seen in the endotoxemic group receiving calcium (p < .008 vs. controls). Total Ca2+ levels in adiposal tissue and skeletal muscle were similar in all groups. Calcium administration did not significantly alter systemic hemodynamics or survival in this model of septic shock (four survivors in the endotoxemic group and five in the calcium administration group). CONCLUSIONS: Endotoxemia in the pig rapidly induced hypocalcemia. Calcium accumulation was found in ascites and in the liver, but not in other examined tissues. Calcium administration, restoring the Ca2+ concentration, did not improve hemodynamics or survival in this model of hypodynamic sepsis. Porcine endotoxemic shock, which replicates human septic shock, seems to be suitable for evaluating calcium turnover.

Animals↗

Communicative development in Swedish children 16-28 months old: the Swedish early communicative development inventory--words and sentences.

To describe the development of words and sentences in Swedish children 16-28 months old, 900 parental reports on 336 children were analyzed. Subjects were randomly selected from the national birth register, and there was a response rate of 88%. The assessments were made using the Swedish Early Communicative Development Inventory--words and sentences (SECDI--w&s). Age-based norms for productive vocabulary, pragmatic skills, grammar skills, and maximum length of utterance (MaxLU) were determined. We describe the development of feedback morphemes, semantic categories, and single words and tasks. Correlation across measures was significant, and especially strong between vocabulary size and grammar skills. Optimized positive predictive values were high for 25 to 28 month predictions (71%-88%), and vocabulary scores were found to be of particular predictive importance. No significant gender differences were detected. The clinical relevance of the instrument is discussed.

Age Factors↗

Epidemiology of pneumococcal infections in Swedish children.

OBJECTIVE: This paper provides an overview of pneumococcal infections in Swedish children. METHOD: Data supplied by the Swedish Institute for Infectious Disease Control (SMI) provided information on invasive pneumococcal isolates and on isolates with reduced susceptibility to penicillin. Disease burden was estimated from data collected in northern Stockholm and Malmöhus County. RESULTS: Only 3-6% of the total number of invasive pneumococcal isolates came from children 0-15 years of age. Predominant serotypes in descending frequency were 7, 6, 14, and 23. Strains from all sources with reduced sensitivity to penicillin (MIC > or = 0.5 mg/l) were found in 3% of children and varied between 0.2% and 11%, with the highest value found in Southern Sweden (predominating strains were 9, 19, 15, 6, and 23). A 10-year review of all cases of meningitis in Northern Stockholm reflected an incidence of 10/100,000 (0-2 years) or 5.8/100,000 (0-5 years), with severe sequelae occurring in 20% of children. This information can be used to predict an annual incidence of 30 cases of meningitis in Sweden. CONCLUSION: The large proportion of serotype 7 among invasive isolates is distressing since this serotype is not represented in the present 7- and 9-valent protein-conjugated vaccines under development. However, the heptavalent vaccine, including serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F would (at a serotype level) provide coverage against 83% of the resistant isolates in Southern Sweden.

Adolescent↗

Occupation and small bowel adenocarcinoma: a European case-control study.

OBJECTIVES: Because of the rarity of small bowel adenocarcinoma (SBA), little is known about the aetiology of this disease. This study aimed to identify occupational clustering of cases SBA as a systematic approach to new hypotheses on the aetiology of this disease. METHODS: A European multicentre case-control study was conducted in 1995-7, inclusive. Incident cases aged 35-69 years with SBA (n=168) were recruited before acceptance by a pathologist. Altogether 107 cases and 3915 controls were accepted, of which 79 cases, 579 colon cancer controls, and 2070 population controls were interviewed. RESULTS: The strongest industrial risk factors for SBA taking account of 10 years' exposure lag were dry cleaning, manufacture of workwear, mixed farming (women), and manufacture of motor vehicles (men). A significantly increased risk of SBA (odds ratio (OR) and 95% confidence interval (95% CI)) was found among men employed as building caretakers, OR 6.7 (1.7 to 26.0) and women employed as housekeepers, OR 2.2 (1.1 to 4.9); general farm labourers, OR 4.7 (1.8 to 12.2); dockers, OR 2.9 (1.0 to 8.2); dry cleaners or launderers, OR 4.1 (1.2 to 13.6); and textile workers (sewers or embroiderers), OR 2.6 (1.0 to 6.8). For the last four groups, together with welders OR 2.7 (1.1 to 6.6) (men) an exposure-response pattern was found when calculating the ORs for jobs held 1-5 years and >5 years, with never having held the job as reference. The ORs (95% CIs) for 1-5 years and >5 years were 4.3 (0.4 to 44.0) and 3.5 (0.9 to 13.7), 3.0 (0.3 to 26.2) and 4.3 (0.9 to 21.2), 4.6 (0.4 to 48.1) and 11.0 (2.0 to 60.4), 1.3 (0.2 to 11.0) and 5.8 (2.0 to 17.2), and 2.8 (0.3 to 23.8) and 4.6 (1.3 to 16.6), respectively, for each of these occupations. Among welders, people performing semiautomatic arc welding (MIG/MAG) were identified as a high risk group (OR 5.0 (1.3 to 19.6)). CONCLUSIONS: This explorative study suggests an increased occurrence of SBA in certain occupations, which needs further evaluation.

Adenocarcinoma↗

Amphetamine abuse during pregnancy: environmental factors and outcome after 14-15 years.

The aim of this study was to assess the influence of social environmental factors on school performance and behavioural problems among 14-year-old children who had been exposed to amphetamine during foetal life. The study group comprised a cohort of 65 children who had suffered intrauterine exposure to amphetamine due to maternal drug abuse. This group has been followed since birth and examined at regular intervals. Information regarding the academic performance of the children was gathered from the school authorities. The psychosocial environment of the children was determined through interviews and through information obtained from the social authorities. Of the 64 children who attended a school within the state school system, 10 (15%) were a year behind for their age. The mean grades were significantly lower than those of their classmates. Behavioural problems were mentioned in the social authority documentation of one-third of the children, regardless of whether the child was placed in a foster home or was residing with the biological mother. A positive significant correlation was found between maternal age and the outcome of the children, as well as between therapy during pregnancy and outcome, whilst several environmental factors, particularly during the child's first four years, correlate negatively to outcome. Psychosocial factors early in life influence the outcome at 14 years. The positive effect of intervention during pregnancy illustrates the importance of early identification preferable during pregnancy.

Adolescent↗

Serum lipid levels associated with increased risk for cardiovascular disease is associated with highly active antiretroviral therapy (HAART) in HIV-1 infection.

The long-term effects of fat metabolism, storage and utilization in HIV-1 infected patients on highly active antiretroviral therapy (HAART) including a protease inhibitor are profound and cause increasing concern. The main importance of these lipid/metabolic disorders lies in their assumed contribution to an increased risk of coronary heart disease (CHD). In the general population increased levels of lipoprotein(a) [Lp(a)] constitute an independent risk factor for CHD by itself as well as in combination with increased levels of cholesterol and low density lipoprotein (LDL)-cholesterol, respectively. Two hundred and fifty-six patients with 27 +/- 7 months HAART and 84 treatment-naive HIV-1 positive patients were screened for cardiovascular risk factors. The subjective perception of fat wasting and/or accumulation in different sites of the body, which was possible to evaluate in 235 patients on HAART and 73 treatment-naive patients, the levels of plasma triglycerides (TG), cholesterol, LDL and high-density lipoproteins (HDL)-cholesterol, LDL/HDL ratio and Lp(a) were measured. Of the patients on HAART, 42% (98/235) reported abnormal fat distribution as compared with 4% (3/73) of the treatment-naive patients (P<0.0001). The levels of TG, cholesterol and LDL-cholesterol, but not HDL-cholesterol or Lp(a) were higher (P<0.0001) in the HAART group as compared with the naive group. Very high Lp(a) levels (> 700 mg/l) were more common among HAART patients as compared with naive, 14% (36/256) vs 2% (2/83); P=0.0022. The Lp(a) levels correlated to the levels of LDL-cholesterol, but not to total cholesterol, HDL-cholesterol or TG, and did not differ between patients with and without subjective perception of abnormal fat distribution. A significant number of the HAART patients had very high levels of Lp(a) and various combinations of increased lipid values associated with considerably increased risk for CHD. The elevation of Lp(a) did not relate to any other clinical or laboratory parameter than to LDL-cholesterol.

Adult↗

Prevalence and risk factors for prelabor rupture of the membranes (PROM) at or near-term in an urban Swedish population.

AIMS: To determine the prevalence, recurrence rate and to identify risk factors for prelabor rupture of the membranes (PROM) after 34 completed weeks in an urban Swedish population. METHODS: In a retrospective cohort study a sample of 2880 women aged 25-41 years, resident in the city of Göteborg, was randomly selected from the population register. According to information from the national Medical Birth Register (MBR), 1507 of these 2880 women had given birth 2736 times. 2270 of these deliveries had occurred in hospitals in the city of Göteborg and case records for 2242 of these deliveries were found. The case records were systematically analyzed for the occurrence of PROM and potential risk factors for PROM. 2208 of these deliveries occurred after 34 weeks of gestation. The further analyses were based on these 2208 deliveries. RESULTS: The prevalence of PROM after 34 week of gestation in this urban Swedish population was 12.9% and about 20% of the women in the population had experienced PROM at least once. In the multiple stepwise regression analysis, risk factors for PROM were primiparity, premature contractions, PROM in a previous pregnancy and bleeding in the first trimester. CONCLUSIONS: PROM is a common complication at or near term. The risk factors for PROM found in this representative study are difficult to influence and thus provide no guidance about how pregnancies should be managed to reduce the occurrence of PROM in the future.

Adult↗

Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock.

Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

Animals↗

Heat shock factor 2 is activated during mouse heart development.

Two members of the heat shock transcription factor family, HSF1 and HSF2, have been identified as activators of mammalian heat shock gene expression. HSF1 acts as a classical stress-responsive factor, whereas HSF2 might play a role in embryogenesis, since it is active during pre- and post-implantation periods up to 15.5 days of mouse embryonic development. In this study, we analyzed HSF1 and HSF2 expression and activation during mouse heart formation. Our results show an abundant expression of HSF1 throughout heart development. In contrast, expression of the alternatively spliced HSF2-alpha and HSF2-beta, and an additional higher molecular weight isoform is strongly upregulated in the developing mouse heart at E11.5-12.5, a stage after which tubular heart has looped and chambers formed, and the myocardial walls are maturating and the valves differentiating. At the same developmental stage, HSF2 DNA-binding activity is transiently induced, whereas the weak HSE-binding activity, which is detected throughout heart development, consists primarily of HSF1. Interestingly, heat shock gene expression shows no temporal or spatial correlation with HSF2 expression and activation. Taken together, our results indicate that HSF2 activation is associated with specific stages of heart formation but is not involved in the regulation of inducible heat shock gene expression.

Alternative Splicing↗

Occupational exposures and risk of gastric cancer in a population-based case-control study.

Gastric cancer trends seem to follow improvements in the environment of blue-collar workers, but the etiological role of occupational exposures in gastric carcinogenesis is scantily investigated. The risk of gastric adenocarcinoma in 10 common occupational industries, and particularly the long-term effects of asbestos, organic solvents, impregnating agents, insecticides, and herbicides, were evaluated in a population-based case-control study, including data on most established risk factors. The study base included all individuals of ages 40-79, born in Sweden and living in either of two areas (total population, 1.3 million) with differing gastric cancer incidences, from February 1989 through January 1995. We interviewed 567 cases classified to site (cardia/noncardia) and histological type, and 1,165 population-based controls, frequency-matched for age and sex. Metal workers had a 46% excess gastric cancer risk [adjusted odds ratio (OR), 1.46; 95% confidence interval (CI), 1.10-1.94], increasing to 1.65 (95% CI, 1.17-2.32) for >10 years in the industry. The elevated risk after exposure to herbicides (OR, 1.56; 95% CI, 1.13-2.15) was attributable to phenoxyacetic acids (adjusted OR, 1.70; 95% CI, 1.16-2.48), similarly across tumor subtypes, and not modified by smoking, body mass index, or Helicobacter pylori. The absence of interaction was demonstrated by the pure multiplicative effect found among those exposed to both H. pylori and phenoxyacetic acids (OR, 3.42; 95% CI, 1.41-8.26). Organic solvents, insecticides, impregnating agents, and asbestos were not associated with gastric cancer risk. Employment in the metal industry and exposure to phenoxyacetic acids were both positively and independently associated with gastric cancer risk. The fractions of all gastric cancers attributable to these job-related exposures were small but not negligible (7 and 5%, respectively) in the Swedish population.

Adenocarcinoma↗

Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets.

Inhibitory receptors expressed on natural killer (NK) cells abrogate positive signals upon binding corresponding major histocompatibility complex (MHC) class I molecules on various target cells. By directly micromanipulating the effector-target cell encounter using an optical tweezers system which allowed temporal and spatial control, we demonstrate that Ly49-MHC class I interactions prevent characteristic cellular responses in NK cells upon binding to target cells. Furthermore, using this system, we directly demonstrate that an NK cell already bound to a resistant target cell may simultaneously bind and kill a susceptible target cell. Thus, although Ly49-mediated inhibitory signals can prevent many types of effector responses, they do not globally inhibit cellular function, but rather the inhibitory signal is spatially restricted towards resistant targets.

Animals↗

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Journal Article↗

Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans.

BACKGROUND: Apolipoprotein (apo) A-I is the major protein component of HDL, a cholesterol transport particle that protects against atherosclerosis. Apo A-I is believed to promote reverse cholesterol transport, transferring cholesterol from peripheral cells to the liver for subsequent elimination. To test this hypothesis in humans, we measured fecal steroid excretion before and after the intravenous infusion of human proapo A-I (precursor of apo A-I) liposome complexes. METHODS AND RESULTS: Four subjects with heterozygous familial hypercholesterolemia w re studied under standardized conditions. The fecal excretion of bile acids and neutral sterols was determined for 9 days before and 9 days after an intravenous infusion of recombinant human proapo A-I (4 g protein) liposome complexes. Plasma apoA-I and HDL cholesterol levels increased transiently (mean peak concentrations were 64% and 35% above baseline, respectively) during the first 24 hours. Mean lipoprotein lipid and apolipoprotein levels were not different during the 2 collecting periods, however. Serum lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, was also unchanged. The fecal excretion of cholesterol (neutral sterols and bile acids) increased in all subjects (mean increase, +39% and +30%, respectively), corresponding to the removal of approximately 500 mg/d excess cholesterol after infusion. Control infusions with only liposomes in 2 of the patients did not influence lipoprotein pattern or cholesterol excretion. CONCLUSIONS: Infusion of proapoA-I liposomes in humans promotes net cholesterol excretion from the body, implying a stimulation of reverse cholesterol transport. This mechanism may prove useful in the treatment of atherosclerosis.

Adult↗

Evidence for 4-hydroxyproline in viral proteins. Characterization of a viral prolyl 4-hydroxylase and its peptide substrates.

4-Hydroxyproline, the characteristic amino acid of collagens and collagen-like proteins in animals, is also found in certain proline-rich proteins in plants but has been believed to be absent from viral and bacterial proteins. We report here on the cloning and characterization from a eukaryotic algal virus, Paramecium bursaria Chlorella virus-1, of a 242-residue polypeptide, which shows distinct sequence similarity to the C-terminal half of the catalytic alpha subunits of animal prolyl 4-hydroxylases. The recombinant polypeptide, expressed in Escherichia coli, was found to be a soluble monomer and to hydroxylate both (Pro-Pro-Gly)(10) and poly(L-proline), the standard substrates of animal and plant prolyl 4-hydroxylases, respectively. Synthetic peptides such as (Pro-Ala-Pro-Lys)(n), (Ser-Pro-Lys-Pro-Pro)(5), and (Pro-Glu-Pro-Pro-Ala)(5) corresponding to proline-rich repeats coded by the viral genome also served as substrates. (Pro-Ala-Pro-Lys)(10) was a particularly good substrate, with a K(m) of 20 microM. The prolines in both positions in this repeat were hydroxylated, those preceding the alanines being hydroxylated more efficiently. The data strongly suggest that P. bursaria Chlorella virus-1 expresses proteins in which many prolines become hydroxylated to 4-hydroxyproline by a novel viral prolyl 4-hydroxylase.

Amino Acid Sequence↗

A case-control study of non-Hodgkin lymphoma and exposure to pesticides.

BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased in most Western countries during the last few decades. Immunodefective conditions are established risk factors. In 1981, the authors reported an increased risk for NHL following exposure to certain pesticides. The current study was designed to further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL. METHODS: A population-based case-control study in northern and middle Sweden encompassing 442 cases and twice as many controls was performed. Exposure data were ascertained by comprehensive questionnaires, and the questionnaires were supplemented by telephone interviews. In total, 404 cases and 741 controls answered the questionnaire. Univariate and multivariate analyses were performed with the SAS statistical data program. RESULTS: Increased risk for NHL was found for subjects exposed to herbicides (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.5) and fungicides (OR, 3.7; 95% CI, 1.1-13.0). Among herbicides, the phenoxyacetic acids dominated (OR, 1.5; 95% CI, 0.9-2.4); and, when subclassified, one of these, 4-chloro-2-methyl phenoxyacetic acid (MCPA), turned out to be significantly associated with NHL (OR, 2.7; 95% CI, 1.0-6.9). For several categories of herbicides, it was noted that only exposure during the most recent decades before diagnosis of NHL was associated with an increased risk of NHL. Exposure to impregnating agents and insecticides was, at most, only weakly related to NHL. CONCLUSIONS: Exposure to herbicides in total, including phenoxyacetic acids, during the decades before NHL diagnosis resulted in increased risk for NHL. Thus, the risk following exposure was related to the latency period. Fungicides also increased the risk for NHL when combined, but this group consisted of several different agents, and few subjects were exposed to each type of fungicide.

2-Methyl-4-chlorophenoxyacetic Acid↗