[A case report. H2-antagonist efficient against drug-related weight gain].
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Aged↗
Biomedical subjects
H Eriksson
Publications and source records attributed to H Eriksson.
[Scientific theory and medical research--reflections seen from the perspective of the MFR].
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Education, Medical, Continuing↗
Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors.
BACKGROUND: The recurrence rate after deep vein thrombosis (DVT) is high and the risk factors for recurrent thromboembolic events have only been investigated on a small scale. OBJECTIVES: To estimate the cumulative incidence of recurrent venous thromboembolic events after a first or a second DVT and to identify possible risk factors for recurrent venous thromboembolism. METHODS: We prospectively followed up 738 consecutive patients with an objectively verified symptomatic DVT for 3.7 to 8.8 years. Medical records and death certificates for all patients were reviewed during follow-up and recurrent DVT and pulmonary embolism were registered. RESULTS: The 5-year cumulative incidence of recurrent venous thromboembolic events was 21.5% (95% confidence interval [CI], 17.7%-25.4%) after a first DVT and 27.9% (95% CI, 19.7%-36.1%) after a second DVT. The 5-year cumulative incidence of fatal pulmonary embolism was 2.6% (95% CI, 1.1%-4.1%) after a first DVT. Proximal DVT (relative risk [RR], 2.40; 95% CI, 1.48-3.88; P<.001), cancer (RR, 1.97; 95% CI, 1.20-3.23; P<.001), and history of a venous thromboembolism (RR, 1.71; 95% CI, 1.16-2.52; P<.01) predicted an independently increased risk of recurrent events in multivariate survival analysis. Postoperative DVT (RR, 0.27; 95% CI, 0.13-0.55; P<.001) and a long duration of oral anticoagulation therapy (RR, 0.95; 95% CI, 0.92-0.98; P<.01) involved a smaller risk of recurrent events. Sex, age, initial antithrombotic therapy, or immobilization did not affect the risk of a recurrent event. CONCLUSIONS: The recurrence rate after a symptomatic DVT is high. Patients with proximal DVT, diagnosed cancer, short duration of oral anticoagulation therapy, or a history of thromboembolic events had a higher risk of recurrent events, while patients with postoperative DVT had a lower recurrence rate. This knowledge could help identify patients who might benefit most from prolonged prophylactic treatment in various risk situations.
Adolescent↗
Effects of estradiol and estradiol sulfamate on the uterus of ovariectomized or ovariectomized and hypophysectomized rats.
Estradiol sulfamate (J995), estradiol-17beta with a substituted sulfamate group in position 3, has much higher systemic estrogenic activity after oral administration than 17beta-estradiol (E2) due to reduced hepatic metabolism of the drug. The lower dose necessary for achievement of adequate systemic estrogenic effects results in a substantial reduction of otherwise commonly observed hepatic side-effects. This makes J995 a strong candidate as an estrogen suitable for oral administration. The present study was performed to examine and compare the effects of J995 and E2 on the uterus after oral or subcutaneous administration to ovariectomized or ovariectomized+hypophysectomized female rats, in particular on the levels of the estrogen receptor (ER) (alpha+beta), ERalpha mRNA and insulin-like growth factor-I (IGF-I) mRNA. The ER levels were determined using a ligand binding assay and the mRNA levels using solution hybridization. The doses of J995 or E2 were chosen to achieve comparable uterotrophic activity. The rats were treated with hormones for 7 days and the treatment was initiated 14 days after surgery. We conclude that there are no major differences in the uterine response to treatment with J995 or E2 with respect to the effects on ER and ERalpha mRNA levels. The IGF-I mRNA level though, is more affected by J995 than by E2 after 7 days of treatment, indicating a prolonged effect of J995.
Administration, Oral↗
High fruit intake may reduce mortality among middle-aged and elderly men. The Study of Men Born in 1913.
OBJECTIVE: A number of long-term population-based studies have tried to study fruit and vegetable consumption in relation to cardiovascular disease, cancer and total mortality. Few of these studies are based on randomly selected population samples. The aim of the study was to investigate the long-term effect of fruit and vegetable consumption on mortality, cardiovascular disease, cardiovascular death, cancer morbidity and cancer death among middle-aged and elderly men. DESIGN: Prospective cohort study. SETTING: General community. The Study of Men Born in 1913. SUBJECTS: 792 men at age 54 who participated in a screening examination in 1967. MAIN OUTCOME MEASURES: A food frequency questionnaire was used to obtain information of the dietary habits in 730 of the men (92%). All men were followed up with repeated examinations until the age of 80. RESULTS: Cardiovascular as well as total mortality was significantly lower among men with high fruit consumption in univariate analysis. There was no correlation between fruit or vegetable consumption in relation to cancer incidence, cancer death and cardiovascular disease. In multivariate survival analysis where smoking, cholesterol and hypertension were taken into account, there was a significantly lower mortality among men with a high fruit consumption during 16 y follow up until the age of 70 (P=0.042), but this finding was no longer statistically significant during 26 y follow-up at the age of 80 (P=0.051). CONCLUSIONS: Daily fruit consumption seems to have positive effect on long-term survival independently of other traditional cardiovascular risk factors like smoking, hypertension and cholesterol. SPONSORSHIP: This study was supported by grants from the Swedish Medical Research Council (K98-274-06276-17) King Gustav V and Queen Victoria's Foundation, and the Göteborg University.
Cardiovascular Diseases↗
Secular changes in cardiovascular risk factors over 30 years in Swedish men aged 50: the study of men born in 1913, 1923, 1933 and 1943.
OBJECTIVES: To study secular trends in cardiovascular risk factors in men aged 50 over a period of 30 years. DESIGN: Cross-sectional studies of successive cohorts of men from 1963 to 1993. SETTING: City of Göteborg, Sweden. SUBJECTS: Four random population samples of men born in 1913, 1923, 1933 and 1943, aged 50 when they were examined in 1963, 1973, 1983, and 1993 (n = 855, 226, 776, and 798, respectively). MAIN OUTCOME MEASURES: Anthropometric measurements, blood pressure, serum cholesterol and triglycerides and smoking habits over three decades. RESULTS: Over 30 years, men increased in weight from a mean (SD) of 75.9 (11.0) kg to 82.8 (12.1) kg and gained 3.4 cm in height, with a net increase in body mass index from 24.8 (3.2) to 26.0 (3.4) kg m-2 (P < 0.0001), and a concomitant increase in waist circumference. The proportion of men who were overweight but not obese (BMI = 25-30 kg m-2) increased from 38 to 47%, whereas the prevalence of frank obesity (more than 30 kg m-2) increased from 6% in 1963 to 11% in 1993. Despite the increase in weight, mean systolic blood pressure fell by almost 10 mmHg (P < 0.0001). Mean serum cholesterol concentration decreased from 6.42 (1.12) to 5.88 (1.04) (P < 0.0001). Serum triglycerides increased from 1.26 (0.77) to 1.69 (1.04) mmol L-1 (P = 0.001). The proportion of men who smoked decreased from 56% in 1963 to 30% in 1993 (P < 0.0001). This was due more to an increase in smoking cessation rates than to an increase in the proportion of men who had never smoked. In particular, smokers and former smokers are now more obese than the corresponding categories 30 years ago and smokers are no longer leaner than men who have never smoked. CONCLUSIONS: Over a period of 30 years, serum cholesterol as well as systolic blood pressure and the prevalence of smoking decreased. This favourable decline in coronary risk factors was offset by an appreciable increase in body mass index and waist circumference.
Aged↗
Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden.
OBJECTIVE: To assess the risk of over-diagnosing and over-treating prostate cancer if population-based screening with serum prostate-specific antigen (PSA) is instituted. PATIENTS AND METHODS: From a serum bank stored in 1980, PSA was analysed in 658 men with no previously known prostate cancer from a well-defined cohort from Göteborg, Sweden (men born in 1913); the incidence of clinical prostate cancer was registered until 1995. From the same area, and with the same selection criteria, another cohort of 710 men born in 1930-31, who in 1995 accepted an invitation for PSA screening, was also analysed. RESULTS: Of men born in 1913, 18 (2.7%) had died from prostate cancer and the cumulative probability of being diagnosed with clinical prostate cancer was 11.1% (5.0% in those with a PSA level of < 3 ng/mL vs 32.9% in those with a PSA level of > 3 ng/mL, P < 0.01). The mean lead-time from increased PSA (> 3 ng/mL) to clinical diagnosis was 7 years. The prostate cancer detection rate in men born in 1930-31 was 4.4% (22% among those with increased PSA levels) and 30 of 31 detected cancers were clinically localized. CONCLUSIONS: Screening and sextant biopsies resulted in a lower detection rate (22%) than the cumulative risk of having clinical prostate cancer (33%) in men with increased PSA levels, indicating that under-diagnosis rather than over-diagnosis is the case at least with 'one-time' screening. Even if the stage distribution in screening-detected cancers seems promising (and thus may result in reduced mortality) it is notable that screening 67-year-old men will result in treatment a mean of 7 years before clinical symptoms occur and only one in four men anticipated to develop prostate cancer will die from the disease within 15 years. Large randomized screening trials seem mandatory to further explore the benefits and hazards of PSA screening.
Aged↗
Thioredoxin expression in human myometrium and fibroids.
Thioredoxin is a small multifunctional protein which acts as a dithiol hydrogen donor for ribonucleotide reductase in DNA synthesis. Thioredoxin participates in the regulation of different metabolic processes, such as changes in the activity of different enzymes, receptors or transcription factors. The aim of the present study was to determine possible differences in the expression of thioredoxin between myometrium and fibroids in women during different periods of life. Thioredoxin mRNA concentrations were determined in myometrial and fibroid tissues obtained from women during the menstrual cycle, during treatment with an analogue of gonadotrophin releasing hormone (GnRH agonist), in the postmenopausal period (PMP) and during pregnancy. The concentration of thioredoxin mRNA was measured by a solution hybridization method. The localization of thioredoxin protein was examined by immunohistochemistry. There were significantly lower levels of thioredoxin expression in both fibroids and myometrium from GnRH agonist treated and PMP women in comparison with the pregnant women. No difference in thioredoxin expression was found between myometrium and fibroids from the same woman or between myometria from uteri with or without fibroids in the same patient group. Thioredoxin expression in uterine fibroids does not seem to be up-regulated, but changes in response to the endocrine conditions in a similar way to that observed in the myometrium.
Adult↗
The expression of glutaredoxin is increased in the human cervix in term pregnancy and immediately post-partum, particularly after prostaglandin-induced delivery.
Glutaredoxins are glutathione disulphide oxidoreductases catalysing disulphide reductions via a redox active disulphide. We have examined the presence of glutaredoxin in the human cervix, and its differential expression during cervical remodelling in term pregnancy and immediately post-partum as compared to the non-pregnant state. Cervical biopsies were obtained from 24 term-pregnant and 24 post-partal women, of which 10 were taken after spontaneous delivery, 10 after prostaglandin-induced delivery and four after mifepristone-induced delivery, all obtained within 15 min after delivery. Six non-pregnant women served as controls. The tissues were analysed for the glutaredoxin mRNA levels using a solution hybridization method. Glutaredoxin mRNA was expressed in the human cervix, the level increased > or =2-fold at term pregnancy and immediately post-partum. The level of cervical glutaredoxin mRNA from prostaglandin E(2)-treated women was 3-fold higher than after spontaneous ripening and delivery. Localization of glutaredoxin was visualized with immunohistochemistry in cervices from two post-partal women, and was compared to that of thioredoxin. We conclude that glutaredoxin may be involved in the regulation of cervical ripening in humans, particularly in the inflammatory reaction seen during this process. Glutaredoxin mRNA levels are up-regulated after prostaglandin treatment, which is effective and the most commonly used substance for cervical priming and induction of labour.
Abortifacient Agents, Steroidal↗
Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle.
The action of steroid hormones is primarily mediated via a process that involves hormone binding to specific receptors in target cells, which leads to transcriptional activation of steroid-responsive genes and, subsequently, to a modification of cellular responses. The aim of the present study was to obtain information about the dynamics of the two types of estrogen receptors (ERs), alpha and beta, by comparing their concentration and distribution in the reproductive tract of the rat during the estrous cycle. Twenty-four 55- to 60-day-old female Sprague-Dawley rats were used. The stage of estrous cycle was determined by vaginal smear. ERalpha was the dominating subtype in uterus, oviduct, and cervix/vagina, with the distribution varying in stroma and epithelium during the estrous cycle. A low level of ERalpha mRNA was observed in ovarian stromal cells, with some scattered positive cells found among granulosa cells. ERbeta expression was observed in the different compartments of uterus and cervix/vagina, but cyclic variation during the estrous cycle was less evident than that of ERalpha. Only a few scattered cells that contained ERbeta mRNA were observed in oviduct. ERbeta mRNA was highly expressed in granulosa cells of developing follicles, with a weaker hybridization signal in new corpora lutea. Immunohistochemistry showed that protein levels of ERalpha and ERbeta have distinct specificity for tissues and cell types, similar to their respective levels of mRNA, as assessed by in situ hybridization. The precise physiological function and importance of ERbeta is still unclear. The relative physiological and pathological function of each ER subtype in the female reproductive tract remains to be further evaluated.
Animals↗
Biphasic effects of the natural estrogen 17beta-estradiol on hepatic cholesterol metabolism in intact female rats.
The protective influence of estrogens in cardiovascular disease is believed to be partly due to beneficial effects on cholesterol metabolism. Much of the experimental data are based on models in which synthetic estrogens have been used in pharmacological doses, and therefore, the physiological role of estrogens in cholesterol metabolism is uncertain. To evaluate this important issue, we performed experiments in intact female rats with use of the natural estrogen 17beta-estradiol (E2) administered either subcutaneously or orally. After physiological doses of E2 (< or =0.04 mg. kg(-1). d(-1)) were administered, plasma levels of high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I were increased. In the liver, 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7alpha-hydroxylase activities were increased, as well as cholesterol 7alpha-hydroxylase mRNA levels. These effects were abolished during treatment with higher doses of E2, whereas apo A-I mRNA increased in a dose-dependent way. After treatment with pharmacological doses of E2 (> or =0.2 mg. kg(-1). d(-1)), the number of hepatic low density lipoprotein receptors increased and plasma cholesterol was reduced. These effects were similar after both oral and subcutaneous administration of E2. Our results show that the responses to E2 are biphasic: plasma HDL, apo A-I, and hepatic enzyme activities governing bile acid and cholesterol synthesis increased only at physiological doses of E2. At pharmacological doses of E2, hepatic low density lipoprotein receptors are stimulated and plasma cholesterol is reduced. Therefore, under physiological conditions, E2 exerts its major effects on hepatic cholesterol metabolism through mechanisms other than stimulation of low density lipoprotein receptor expression.
Administration, Oral↗
Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: "the study of men born in 1913".
BACKGROUND: Risk factors for deep vein thrombosis and pulmonary embolism are mostly derived from case-control studies of hospitalized patients, and there are few long-term population-based studies. OBJECTIVE: To study the long-term risk factors for deep vein thrombosis and pulmonary embolism among middle-aged men. DESIGN: A prospective cohort study. SETTING: General community, "The Study of Men Born in 1913." SUBJECTS: A random population sample of 855 men, all aged 50 years at baseline. MAIN OUTCOME MEASURES: Eight-hundred fifty-five men participated in a screening examination in 1963 at the age of 50 years, and 792 of these men were reexamined in 1967 at the age of 54. All the men were followed up with periodic examinations until the age of 80. Objective methods were used to ascertain a diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Waist circumference (P=.004) and smoking (P = .02) predicted a venous thromboembolic event in multivariate survival analysis. Men in the highest decile of waist circumference (> or =100 cm) had an adjusted relative risk of 3.92 (95% confidence interval, 2.10-7.29; P<.001) compared with men with a waist circumference of less than 100 cm. For men who smoked 15 g of tobacco (15 cigarettes) a day or more, the adjusted relative risk was 2.82 (95% confidence interval, 1.30-6.13; P= .009) compared with nonsmokers. CONCLUSIONS: Smoking and abdominal obesity were independent risk factors for venous thromboembolic events during follow-up. In addition to the prevention of smoking and obesity, a more aggressive strategy regarding the use of prophylactic agents among smokers and obese patients, in various risk situations, may be justified.
Abdomen↗
[Nurses working with anticoagulants--a new subspecialty? Time for a new and important kind of training].
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Anticoagulants↗
The cloned guinea pig neuropeptide Y receptor Y1 conforms to other mammalian Y1 receptors.
We have cloned the guinea pig neuropeptide Y (NPY) Y1 receptor and found it to be 92-93% identical to other cloned mammalian Y1 receptors. Porcine NPY and peptide YY (PYY) displayed affinities of 43 pM and 48 pM, respectively. NPY2-36 and NPY3-36 had 6- and 46-fold lower affinity, respectively, than intact NPY. Functional coupling was measured by using a microphysiometer. Human NPY and PYY were equipotent in causing extracellular acidification with EC50 values of 0.59 nM and 0.69 nM, respectively, whereas NPY2-36 and NPY3-36 were about 15-fold and 500-fold less potent, respectively, than NPY. The present study shows that the cloned guinea pig Y1 receptor is very similar to its orthologues in other mammals, both with respect to sequence and pharmacology. Thus, results from previous studies on guinea pig NPY receptors might imply the existence of an additional Y1-like receptor sensitive to B1BP3226.
Amino Acid Sequence↗
Regulation of thioredoxin mRNA in the rat uterus by gonadal steroids.
Estradiol has been shown to increase the level of thioredoxin mRNA in the uterus of the ovariectomized (ovx) rat. In this study the influence of progesterone, androgens, the anti-estrogen ICI 182780 and the anti-androgen Flutamid on thioredoxin expression, has been studied in the rat uterus. Thioredoxin mRNA concentrations were determined by solution hybridization. Ovx rats treated with progesterone alone showed no effect on thioredoxin expression. Combined treatment of ICI 182780 and estradiol attenuated the estradiol-induced increase in thioredoxin mRNA. When ovx rats were treated with a testosterone depot, the amount of thioredoxin mRNA was increased five-fold after 48 h and remained at that level during the rest of the 168 h monitored. A similar increase in thioredoxin mRNA could be seen after 5alpha-dihydrotestosterone treatment, indicating a true androgenic effect. In addition, the anti-androgen Flutamid attenuated the thioredoxin mRNA increase seen after 5alpha-dihydrotestosterone treatment alone. It is concluded that thioredoxin mRNA is regulated by growth promoting gonadal steroids in the rat uterus. The attenuation of the estrogen and androgen-induced increases of the thioredoxin mRNA with ICI 182780 and Flutamid, indicate that the effect is mediated via the estrogen receptor and androgen receptor respectively. None of these hormones affected the hepatic thioredoxin mRNA level in the same animals.
Androgens↗
Prevalence of APC resistance and its relationship to arterial and venous thromboembolism in a general population sample of elderly Swedish men: The Study of Men Born in 1913.
BACKGROUND: Most studies of hereditary resistance to activated protein C (APC resistance) as a risk factor for venous thromboembolism are derived from case-control studies of hospitalized patients, whilst the importance of this condition in the general population has been only sparsely investigated. OBJECTIVE: To study the prevalence of APC resistance and its relationship to morbidity and mortality in a general population sample of elderly men. DESIGN: Cross-sectional and prospective follow-up study. SETTING: General community: The Study of Men Born in 1913. SUBJECTS: A random population sample of 404 men, all 75 years of age. MAIN OUTCOME MEASURES: Four hundred and four men participated in a screening examination in 1988. The APC ratio was analysed in 382 of them. All the men were followed up for 5 years. Medical records were reviewed for all the men with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction or stroke. RESULTS: Twenty-five men (6.5%) were found to have APC resistance. The incidence of venous thromboembolism, myocardial infarction or stroke did not differ between men with or without APC resistance, either retrospectively or during follow-up. Only two men experienced a deep vein thrombosis before the age of 80 and there was no case of pulmonary embolism. Mortality during 5 years of follow-up did not differ between men with and without APC resistance. CONCLUSION: The prevalence of APC resistance was 6.5% in this study of Swedish men. Although the size of the population sample is somewhat small, the study shows that, amongst elderly men, the association between APC resistance and venous thromboembolic disease was weak and men with this hereditary condition did not have any increase in morbidity or mortality compared with men without APC resistance.
Aged↗
Effects of propofol on extracellular acidification rates in primary cortical cell cultures: application of silicon microphysiometry to anaesthesia.
Propofol depresses both cerebral oxygen consumption and glucose utilization. We tested the hypothesis that these well described effects on brain metabolism are manifest by a reduction in neuronal acid production in vitro. The rate of extracellular acidification in primary cell cultures of rat cortical neurones was measured using a novel instrument (silicon microphysiometer) after stimulation with propofol 0.3, 3 and 30 micrograms ml-1. Intralipid 10% served as a control. Propofol 3 micrograms ml-1 caused a mean decrease of 1.51 (SEM 0.71)% in baseline acidification rate, which was significantly greater than that produced by 0.3 microgram ml-1 or Intralipid alone (P < 0.05). The reduction after stimulation with propofol 30 micrograms ml-1 was 4.68 (0.35)% of baseline rates and this in turn was significantly greater than that elicited by propofol 3 or 0.3 microgram ml-1, or Intralipid (P < 0.001). We have confirmed the depressant effect of propofol on cerebral metabolism and established that propofol inhibits neuronal acid excretion in vitro.
Anesthetics, Intravenous↗
A comparative study of estrogen receptors alpha and beta in the rat uterus.
The uterus is an important target organ for steroid hormones. The effects of these hormones are mediated via specific receptors. The aim of this study was to compare the expression, distribution, and regulation of estrogen receptor (ER) alpha and beta in the rat uterus in order to establish possible different biological roles for the two receptor forms. Ovariectomized rats were treated with either estradiol (E(2)), progesterone (P(4)), or combinations of these for 24 or 48 h. The mRNA levels were measured by solution hybridization. Distribution of the mRNAs and receptor proteins was detected by in situ hybridization and immunohistochemistry. The results showed that ERalpha is the dominating subtype in the rat uterus. E(2) seemed to increase the ERalpha mRNA level in the glandular and luminal epithelium, but it caused a decrease of the immunostaining intensity in the glandular epithelium. P(4) reduced ERalpha expression in luminal epithelium whereas no effect was seen in the glandular epithelium. E(2) or P(4) did not alter the expression of ERbeta, on either the mRNA or protein level. In conclusion, the distribution and regulation of ERalpha and ERbeta differ in the different compartments of the rat uterus. The complex uterine responses to E(2) and P(4) are directly or indirectly mediated by differential cell-specific expression of their receptors. The low expression in the uterus and the limited regulation by gonadal steroids in this study suggest that ERbeta probably plays a minor role in the regulation of uterine physiology.
Animals↗