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N Graudal

Publications and source records attributed to N Graudal.

At least 19 recordsLinked to original sources
PubMed2001

Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients.

The object was to analyze, in a nationwide survey, the incidence and course of hereditary hemochromatosis in relation to the degree of iron overload and the presence of organ damage. The study included 179 Danish Caucasian patients with clinically overt hemochromatosis diagnosed between 1948 and 1985. A cohort of 158 patients was followed for a median of 8.5 years (range: 0.2-29.5). From 1951 to 1975, the yearly relative incidence rate was constant: 0.58/100,000 persons >20 years of age. From 1981 to 1985, the yearly relative incidence rate rose to 1.40/100,000 persons >20 years of age. Survival was reduced in the entire series when compared with a matched control population ( p<0.0001). There was a steady increase in survival from 1948 to 1985 ( p<0.002). Survival was significantly reduced in patients with liver cirrhosis and/or diabetes mellitus ( p<0.01). In contrast, survival in patients without cirrhosis or diabetes was similar to rates expected. Survival in patients with arthropathy was higher than in patients without joint affection ( p<0.004). Patients adequately treated with phlebotomy ( n=66) had a higher survival than inadequately treated patients ( n=62; p<0.0001). Adequately treated patients with cirrhosis and/or diabetes had better survival than inadequately treated patients with similar organ damage ( p<0.001). The main causes of death were hepatic failure due to cirrhosis (32.0%) and cirrhosis with liver cancer (23.1%). Sharpened diagnostic awareness has improved early diagnosis and increased the diagnostic frequency of clinical hemochromatosis. Adequate phlebotomy treatment was the major determinant of survival and markedly improved prognosis. Early detection and treatment of this common iron overload disorder is crucial and can completely prevent any excess mortality caused by hemochromatosis.

Adult↗
PubMed2000

Should dietary salt restriction be a basic component of antihypertensive therapy?

The general intake of salt (sodium chloride) is much higher than the recommended allowances, in part because of added salt in food industry processed food. However, population studies have not been able to show an association between salt intake and unfavorable health outcome. Based on population studies and randomized studies, the effect of an extreme salt reduction of 100 mmol on blood pressure in hypertensive persons is about one third of the effect of antihypertensive medications. This effect-size estimate is based on single measurements of blood pressure and is probably overestimated compared with 24-hour blood pressure measurements. Salt reduction has effects on heart rate and serum levels of renin, aldosterone, catecholamines, and lipids that may be unfavorable. Because of insufficient compliance, extreme salt reduction can only be obtained if salt in food industry processed food is eliminated. The full consequences of such elimination are not known. Other nonpharmacological interventions, such as weight reduction and diets including fruits, vegetables, and low-fat dairy foods, are probably easier to implement and more effective to decrease blood pressure than salt reduction. Furthermore, salt reduction does not seem to add to the effect size when combined with other nonpharmacological interventions. Salt sensitivity due to sodium channel mutations has been shown in a minority of blacks but not in Caucasians. In conclusion, at present, dietary salt restriction should not be a basic component of antihypertensive therapy.

Adult↗
PubMed2000

Inflammatory patterns in rheumatoid arthritis estimated by the number of swollen and tender joints, the erythrocyte sedimentation rate, and hemoglobin: longterm course and association to radiographic progression.

OBJECTIVE: To investigate the association of individual plots and time-integrated values of repeated measures of inflammatory variables with radiographic outcome in rheumatoid arthritis (RA). METHODS: In 112 patients with RA, examinations of joint swelling and joint tenderness of 68 joints, and measurement of hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) were performed each year for up to 22 years after the first visit. For each of these 4 variables, the patients were divided arbitrarily into 5 characteristic subgroups by means of inspection of individual plots of longitudinal observations of the variables and divided into 5 other subgroups according to 20% percentiles of the cumulative mean values of the variables. The outcome of the subgroups was evaluated by varying degrees of radiographic events estimated by Larsen scoring of consecutive radiographs of 46 joints. RESULTS: An increasing number of radiographic events in subgroups with increasing severity (increasing values of joint swelling, joint tenderness, and ESR, decreasing values of Hb) was seen for both the arbitrary subgroups and the percentile subgroups of joint swelling, Hb, and ESR, whereas the association of joint tenderness to radiographic progression was weak. CONCLUSION: A highly significant association between inflammatory variables and radiographic outcome could be observed, indicating that the degree of inflammation is important for the development of destructive joint damage in RA.

Adolescent↗
PubMed2000

Diagnostic value of routine radioisotope bone scanning in a series of 63 patients with pulmonary sarcoidosis.

BACKGROUND AND AIM: Routine use of diagnostic radioisotope bone scanning in patients with sarcoidosis has not previously been evaluated. The aim of this study was to assess whether routine radioisotope bone scanning might be of value in the detection of osseous lesions in sarcoidosis. METHODS: 63 consecutive Caucasian patients (32 men) with a median age of 39 years (range 17-66) and biopsy proven pulmonary sarcoidosis were included. None had symptoms suggesting osseous sarcoidosis. Extrathoracic, non-osseous sarcoidosis was present in 24 patients; 13 patients were on oral steroids. Radioisotope bone scanning was performed with a gammacamera after intravenous injection of 99mTechnetium-methylenediphosphonate. An abnormal bone scan was followed by a radiograph of the region of interest. RESULTS: 39 patients (61.9%) had normal bone scans. Minor bone scan abnormalities were found in 24 patients (38.1%). Of these, 11 patients had bone foci (8 in the vertebral spine, 9 in the ribs, 1 in a finger). Radiographically only one of these 11 patients had a bony lesion being typical of sarcoidosis, located in the second finger. 17 patients had joint foci. Radiographs of the joints showed sequelae after a fracture in 1 patient, and degenerative osteoarthritis in 1 patient. There was no difference between clinical and paraclinical variables in patients with normal and abnormal bone scans. CONCLUSIONS: There appears to be no indication for routine radioisotope bone scanning in patients with sarcoidosis. Scanning should be restricted to patients with clinical suspicion of osseous sarcoidosis.

Adult↗
PubMed1999

Iron status in Danes updated 1994. I: prevalence of iron deficiency and iron overload in 1332 men aged 40-70 years. Influence Of blood donation, alcohol intake, and iron supplementation.

Iron status, S-ferritin, and hemoglobin (Hb) were assessed in a population survey in 1994 (DAN-MONICA 10) comprising 1332 Caucasian Danish men equally distributed in age cohorts of 40, 50, 60 and 70 years. Blood donors (n=186) had lower S-ferritin, median 76 microg/l, than nondonors, median 169 microg/l (p<0.0001). S-ferritin in donors was inversely correlated with the number of phlebotomies (r(s)=-0.57, p<0.0001). S-ferritin in nondonors (n=1146) was similar in men 40-60 years of age, median 176 microg/l, and subsequently decreased at 70 years of age to a median of 146 microg/l (p=0.01). In the entire series, the prevalence of small iron stores (S-ferritin 16-32 microg/l) was 2.7%, that of depleted iron stores (S-ferritin <16 microg/l) 0.45%, and that of iron deficiency anemia (S-ferritin <13 microg/l and Hb <129 g/l) 0.15%. Among nondonors, the prevalence of iron overload (S-ferritin >300 microg/l) was 20%. S-ferritin in nondonors correlated with body mass index (r(s)=0.19, p=0.0001) and with alcohol intake (r(s)=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14 mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136 microg/l, than nontreated, median 169 microg/l (p<0.001) and those treated with H(2)-receptor antagonists (n=30) had lower S-ferritin, median 142 microg/l, than nontreated, median 171 microg/l (p<0.04). Compared with the DAN-MONICA 1 iron status survey of Danish men in 1984, the prevalences of iron depletion and iron deficiency anemia are unchanged whereas the prevalence of iron overload has increased significantly. In Denmark, iron fortification of flour was abolished in 1987. This apparently had no negative effect on iron status in men.

Adult↗
PubMed1999

A longitudinal study of serum ferritin in 319 adolescent Danish boys and girls examined in 1986 and 1992.

This study examined trends in iron status in adolescents. Serum ferritin was measured in 1986 and 1992 in 319 Danes (161 males) stratified into 5 groups: I. median age 9 yr in 1986 vs. 15 yr in 1992; II. 11 vs. 17 yr; III. 13 vs. 19 yr; IV. 15 vs. 21 yr; V. 17 vs. 23 yr. Males in group I demonstrated no change in ferritin or estimated iron stores in mg/kg; groups II-V displayed an increase in iron status parameters. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in group III, and positively correlated with height velocity in group V. Females in age groups I and II demonstrated a fall in ferritin and estimated iron stores in mg/kg in association with menarche; values were unchanged in groups III and IV, and increased in group V. All groups showed an increase in estimated total iron stores. Changes in iron status parameters were inversely correlated with height velocity in groups I and II. In conclusion, ferritin levels in adolescents display great variation during growth spurt and at menarche. Changes in ferritin showed no consistent association with growth velocity. In both genders, estimated total iron stores increased with age.

Adolescent↗
PubMed1999

Iron status and iron balance during pregnancy. A critical reappraisal of iron supplementation.

BACKGROUND: Iron supplementation in pregnancy is a controversial issue. The aim of this review was to summarize the results of relevant papers on this subject. METHODS: Placebo-controlled studies on iron treatment in pregnancy were identified from the Cochrane database. RESULTS: Among fertile women, 20% have iron reserves of >500 mg, which is the required minimum during pregnancy; 40% have iron stores of 100-500 mg, and 40% have virtually no iron stores. The demand for absorbed iron increases from 0.8 mg/day in early pregnancy to 7.5 mg/day in late pregnancy. Dietary iron intake in fertile women is median 9 mg/day, i.e. the majority of women have an intake below the estimated allowance of 12 18 mg/day. Iron absorption increases in pregnancy, but not enough to prevent iron deficiency anemia in 20%, of women not taking supplementary iron. Iron-treated pregnant women have greater iron reserves, higher hemoglobin levels, and a lower prevalence of iron deficiency anemia than placebo-treated women both in pregnancy as well as postpartum. Furthermore, children born to iron-treated mothers have higher serum ferritin levels than those born to placebo-treated mothers. An iron supplement of 65 mg/day from 20 weeks of gestation is adequate to prevent iron deficiency anemia. CONCLUSIONS: In order to avoid iron deficiency in pregnancy, prophylactic iron supplement should be considered. Iron supplements may be administered on a general or selective basis. The selective approach implies screening with serum ferritin in early pregnancy, in order to identify women who can manage without prophylactic iron.

Adult↗
PubMed1997

Serum erythropoietin during normal pregnancy: relationship to hemoglobin and iron status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women.

Serum erythropoietin (EPO) and its relationship to hemoglobin (Hb), iron status markers and iron supplementation during normal pregnancy was assessed in a longitudinal, placebo-controlled study on 118 women, 61 took daily tablets containing 66 mg ferrous iron from the second trimester until delivery and 57 took placebo. Blood samples were obtained at 4-week intervals until delivery as well as post-partum. In the placebo-treated women, median serum EPO rose from 22.5 U/l at inclusion to 35.0 U/l at delivery (P = 0.0001). In the iron-treated women, median serum EPO rose from 23.9 to 29.9 U/l (P = 0.0001). Serum EPO showed a steeper increase in the placebo-treated women than in the iron-treated women (P < 0.05). After delivery, serum EPO became normal in both groups (P = 0.0001). Median Hb was lower in placebo-treated (iron depleted) than in iron-treated (iron repleted) women (P < 0.05). In the placebo-treated women there was a negative correlation and in the iron-treated women a positive correlation between serum EPO and Hb. In the placebo-treated women, inverse correlations existed between serum EPO and serum transferrin saturation and serum ferritin, reflecting the consequences of iron deficiency, whereas the iron-treated women displayed no correlation. A physiological, nonhypoxia-induced increase in EPO production accounts for the basic expansion of the red cell mass during pregnancy. In placebo-treated women, iron deficient erythropoiesis constitutes an additional hypoxic stimulus, which induces a further increase in serum EPO.

Anemia, Hypochromic↗
PubMed1997

Iron status in young Danes. Evaluation by serum ferritin and haemoglobin in a population survey of 634 individuals aged 14-23 yr.

Iron status was assessed by serum ferritin and haemoglobin in a population survey comprising 634 randomly selected urban Danes (312 males, 322 females) 14-23 yr old. At all ages, males had significantly higher serum ferritin and haemoglobin values than females. Males: median serum ferritin displayed a steady increase with age from 33 to 109 micrograms/l (rs = 0.53, p < 0.0001). The prevalence of absent mobilizable body iron stores (serum ferritin < 13 micrograms/l) was 3.5% at 16-17 yr of age, gradually declining to 0% at 22-23 yr. None of the males had iron deficiency anaemia (serum ferritin < 13 micrograms/l and haemoglobin < 129 g/l). Females: median ferritin values displayed a slight increase with age from 28 to 39 micrograms/l (rs = 0.19, p < 0.001). The prevalence of absent iron stores was 12.5% at 16-17 yr of age, declining to 6.6% at 22-23 yr. The prevalence of iron deficiency anaemia (serum ferritin < 13 micrograms/l and haemoglobin < 121 g/l) was 4.7% at 16-17 yr of age, declining to 1.3% at 22-23 yr of age. Compared with surveys in other parts of Scandinavia, young Danes had slightly higher serum ferritin levels, and a lower prevalence of iron deficiency.

Adolescent↗
PubMed1997

Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to infection and increased mortality.

BACKGROUND: Acquired deficiencies of certain complement proteins and impaired opsonisation activity have been implicated in the pathogenesis of the increased susceptibility to infections of patients with alcoholic cirrhosis. METHODS: Serum concentrations of C3 and C4, plasma concentrations of C3bc, C9, and the terminal C5b-9 complement complex (TCC), and haemolytic complement activity (classic and alternative pathway) of serum, and serum opsonic activity were determined in 46 patients with compensated alcoholic cirrhosis, 31 who were decompensated, and in 15 healthy subjects. After 19 months (median) the investigated variables were analysed for their use in prognosis of recurrent infections and survival. RESULTS: C3 and C4 concentrations and the haemolytic complement activity of the alternative pathway were decreased in decompensated cirrhotic patients compared with controls (p < 0.01). Univariate analysis (log rank test) showed that low concentrations (< or = lower quartile) of C3 (p < 0.001) and C3bc (p < 0.05), haemolytic complement activity of the alternative pathway (p < 0.01) and classic pathway (p < 0.05), and decompensated cirrhosis (p < 0.001) were associated with an increased risk of infection and increased mortality. Multivariate (Cox) analysis showed that low C3 concentrations and decompensation of cirrhosis were significant predictors of infections and mortality (p < 0.02). CONCLUSIONS: Low serum C3 concentrations and decreased haemolytic complement function predisposes to infection and increased mortality in patients with alcoholic cirrhosis.

Adult↗
PubMed1996

Cord serum erythropoietin in 90 healthy newborn term infants: relationship to blood gases and iron status markers.

In this study, we examined the cord serum erythropoietin (EPO) level in newborn infants in relation to venous cord blood gases and iron status markers (cord serum ferritin, cord serum transferrin saturation). The subjects were 90 healthy newborn term infants with a normal birth and 90 healthy women with an uncomplicated pregnancy and delivery. Within 14-18 weeks of gestation, 47 prospective mothers, allocated at random, received tablets containing 66 mg ferrous iron daily, and 43 received a placebo. Serum EPO was measured in women prior to delivery. Serum EPO, serum ferritin and serum transferrin saturation were analyzed in cord blood from the newborn. Blood gases (PO2, PCO2 and standard HCO3, PH) were measured in venous cord blood and Apgar scores were recorded. The cord serum EPO level in the newborn was not significantly affected by the iron supplementation to the mothers. In the entire series, the geometric mean cord serum EPO was 36 U/I, (median 32 U/I, 5-95% 16-150, range 12-380). There was no correlation between cord serum EPO and APgar score, cord blood PO2, PCO2, standard HCO3 and pH. In the newborn of placebo-treated mothers, log cord serum EPO was inversely correlated with log cord serum ferritin (r = -0.54, P < 0.0002) and cord serum transferrin saturation (r = -0.39, P < 0.011), suggesting that iron deficiency may occur in this newborn group.

Apgar Score↗
PubMed1996

Anti-interleukin-6 autoantibodies in plasma are associated with an increased frequency of infections and increased mortality of patients with alcoholic cirrhosis.

Altered cytokine metabolism has been implicated in the pathogenesis of alcoholic liver disease. Recently, autoantibodies to cytokines have been proposed to act as modifiers of cytokine functions. In this study plasma levels of anti-interleukin-1 alpha (IL-1 alpha autoantibodies and anti-IL-6 autoantibodies were determined by RIAs in 96 patients with alcoholic cirrhosis and in 16 healthy individuals. After 19 months (median) the prognostic significance of the cytokine autoantibodies was investigated using univariate analysis (Log-rank test) and multivariate regression analysis (Cox model). The seroprevalences of anti-IL-1 alpha autoantibodies and anti-IL-6 autoantibodies (42 and 18%, respectively) in the patients were not different from healthy individuals and did not relate to severity of liver disease. The presence of anti-IL-1 alpha autoantibodies was of no prognostic significance. Independent of severity of liver disease, patients with anti-IL-6 autoantibodies in plasma had a higher risk of acquiring infections and higher risk of death (P < 0.02) compared to patients without anti-IL-6 autoantibodies. The authors concluded that anti-IL-6 autoantibodies are associated with increased mortality when present in the plasma of patients with alcoholic cirrhosis, which is probably secondary to recurrent infections, but not to underlying severity of liver disease.

Adult↗
PubMed1996

Serum clusterin and vitronectin in alcoholic cirrhosis.

Clusterin and vitronectin are multifunctional regulatory proteins which both serve as complement lysis inhibitors. Previous data have strongly suggested that serum vitronectin is mainly produced in the liver, whereas the biosynthetic origin for serum clusterin has not been determined. In the present study we aimed to determine the role of the liver in producing these proteins and to evaluate the proteins as possible markers of liver failure. We therefore quantified clusterin and vitronectin in serum from patients suffering from alcoholic liver cirrhosis (n = 83), and in serum-free culture supernatants from the hepatoma cell line HepG2. The median clusterin concentration was 0.20 g/l in cirrhosis and 0.37 g/l in the controls, whereas corresponding vitronectin values were 0.19 and 0.26 g/l, respectively. The concentration of both proteins showed significant correlation (p < 0.0001) with disease severity and with established plasma markers of hepatic synthetic function, such as albumin and prothrombin complex. The clusterin level, but not the vitronectin level, correlated with survival (p = 0.005). The rates of synthesis of clusterin, vitronectin and C3 from HepG2 cells were 0.02, 0.21 and 1.9 micrograms/10(6) cells/24 h, respectively. From the present data we conclude that clusterin (as vitronectin and C3) is mainly produced in the liver and may be a useful marker in the evaluation of severity of liver disease and prognosis of patients with alcoholic cirrhosis.

Adult↗
PubMed1996

Distribution of liver haemosiderin iron in 187 patients with various types of hepatic diseases.

The purpose of this study was to evaluate the distribution of haemosiderin iron in various regions of the liver (central, intermediary and peripheral hepatocytes, Kupffer cells, portal macrophages and bile duct epithelial cells) in 174 patients with different hepatic diseases (alcoholic cirrhosis (n = 49), alcoholic steatosis (n = 60), non-alcoholic cirrhosis (n = 16), acute hepatitis (n = 20), clinically overt untreated hereditary haemochromatosis (n = 3), miscellaneous disorders (n = 26)), and in 13 subjects with a normal liver biopsy. Furthermore, the relationship between liver haemosiderin iron, biochemical iron status markers and biochemical liver tests was investigated. In haemochromatosis iron was consistently present in all examined regions of the liver, and in 43% of patients with alcoholic liver disease haemosiderin was present in at least one region of the liver lobule. In 65% of patients with acute hepatitis, haemosiderin was present in macrophages and Kupffer cells. In other hepatic diseases and in normal livers, haemosiderin was rarely seen. Regression analyses showed a correlation between iron status markers in most patients, except in those with high serum aspartate aminotransferase levels. In conclusion, haemosiderin iron is distributed in a typical pattern in haemochromatosis, alcoholic liver disease and acute hepatitis. Both histochemical liver iron and serum ferritin are of value as indirect markers of liver iron stores in patients with moderate hepatocellular damage.

Adolescent↗
PubMed1995

Aminoglycosides: single or multiple daily dosing? A meta-analysis on efficacy and safety.

A number of randomised studies indicate that a single high dose of aminoglycoside every 24 h may be more efficient and less toxic than the same dose divided into multiple daily doses. In the meta-analysis of 16 studies described here, which included more than 1200 patients, the relative chance (i.e. the relative risk, RR) of cure of the single-dose regime compared with the multiple-dose regime was 1.027, indicating that the single daily dose regime had a 2.7% higher cure rate (NS). The RR of avoiding nephrotoxicity was 1.001 (NS) and the RR of avoiding ototoxicity was 1.001 (NS). It is concluded that there is no difference concerning efficacy and safety between single-dose and multiple-dose regimes for administration of aminoglycosides.

Aminoglycosides↗
PubMed1995

Iron status markers during pregnancy. No relationship between levels at the beginning of the second trimester, prior to delivery and post partum.

OBJECTIVE: To evaluate whether levels of iron status markers (haemoglobin, serum transferrin saturation, serum ferritin) in pregnant women, measured in the beginning of the second trimester, could be used to predict levels later in pregnancy, pre partum and post partum. DESIGN: Randomized, double-blind, placebo-controlled parallel study. SETTING: The Birth Clinic at the Department of Obstetrics, Herning Hospital, Herning, Denmark. SUBJECTS: One hundred and twenty healthy pregnant women between 14 and 18 weeks of gestation. INTERVENTIONS: Sixty-three women were allocated to treatment with tablets containing 66 mg ferrous iron (as fumarate) daily, and 57 women to treatment with placebo. MAIN OUTCOME MEASURES: Haemoglobin, serum transferrin saturation, and serum ferritin were measured every 4th week during gestation, prior to delivery, and 1 and 8 weeks post partum. RESULTS: Correlation matrices during pregnancy and post partum were calculated for each iron status marker separately in iron-treated and placebo-treated women. Haemoglobin, transferrin saturation and serum ferritin values at inclusion displayed steadily declining correlation coefficients with values obtained later in pregnancy. There were no clinically relevant correlations to values obtained 8 weeks or less prior to delivery, and no correlations to values post partum. Serum ferritin values at inclusion could not be used to predict values later in pregnancy or post partum. CONCLUSION: Haemoglobin, transferrin saturation and serum ferritin values measured in the beginning of the second trimester appear to be unsuitable as guidelines for an individual iron prophylaxis in pregnant women.

Adult↗
PubMed1995

Mannan-binding protein and complement dependent opsonization in alcoholic cirrhosis.

Mannan-binding protein is synthesized by the liver and functions in first-line host defence by opsonizing mannose-rich microorganisms due to activation of the classical complement pathway independent of Clq, and by an intrinsic ability to opsonize and mediate phagocytosis. We have investigated whether the increased susceptibility to bacterial infections in patients with cirrhosis could be explained by low plasma concentrations of mannan-binding protein and impaired complement-dependent opsonization. We examined 51 patients with compensated alcoholic cirrhosis, 34 who were decompensated and 16 healthy controls. Irrespective of group, we found a significant correlation (p < 0.05) between plasma mannan-binding protein concentration and deposition of the complement opsonin C4 on mannan from baker's yeast. In contrast to what was expected, this kind of opsonization and plasma levels of mannan-binding protein were significantly increased in the patients with decompensated cirrhosis (p = 0.01 and p = 0.007, respectively). A significant correlation (0 < 0.05) was found between mannan-binding protein and erythrocyte sedimentation rate, fibrinogen and haptoglobin in these patients. Though the correlations were weak (rho = 0.49, rho = 0.48 and rho = 0.40, respectively), the elevated levels of mannan-binding protein in the patients with decompensated cirrhosis may reflect an acute phase reaction. It is concluded that plasma levels of mannan-binding protein are increased in patients with decompensated cirrhosis and that complement-dependent opsonization of mannan does not seem to be compromized in patients with alcoholic cirrhosis.

Adult↗