Niels Graudal

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

Abstract. 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 8.5xa0years (range: 0.2–29.5). From 1951 to 1975, the yearly relative incidence rate was constant: 0.58/100,000 persons >20xa0years of age. From 1981 to 1985, the yearly relative incidence rate rose to 1.40/100,000 persons >20xa0years 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.

Iron prophylaxis during pregnancy - How much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

Objective.u2002 To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.

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.

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

Abstractu2002Iron 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 70u2009years. Blood donors (n=186) had lower S-ferritin, median 76u2009μg/l, than nondonors, median 169u2009μg/l (p<0.0001). S-ferritin in donors was inversely correlated with the number of phlebotomies (rs=–0.57, p<0.0001). S-ferritin in nondonors (n=1146) was similar in men 40–60u2009years of age, median 176u2009μg/l, and subsequently decreased at 70u2009years of age to a median of 146u2009μg/l (p=0.01). In the entire series, the prevalence of small iron stores (S-ferritin 16–32u2009μg/l) was 2.7%, that of depleted iron stores (S-ferritin <16u2009μg/l) 0.45%, and that of iron deficiency anemia (S-ferritin <13u2009μg/l and Hb <129u2009g/l) 0.15%. Among nondonors, the prevalence of iron overload (S-ferritin >300u2009μg/l) was 20%. S-ferritin in nondonors correlated with body mass index (rs=0.19, p=0.0001) and with alcohol intake (rs=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14u2009mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136u2009μg/l, than nontreated, median 169u2009μg/l (p<0.001) and those treated with H2-receptor antagonists (n=30) had lower S-ferritin, median 142u2009μg/l, than nontreated, median 171u2009μg/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.

Normal Range of Human Dietary Sodium Intake: A Perspective Based on 24-Hour Urinary Sodium Excretion Worldwide

BACKGROUNDnThe recommendation to restrict dietary sodium for management of hypertensive cardiovascular disease assumes that sodium intake exceeds physiologic need, that it can be significantly reduced, and that the reduction can be maintained over time. In contrast, neuroscientists have identified neural circuits in vertebrate animals that regulate sodium appetite within a narrow physiologic range. This study further validates our previous report that sodium intake, consistent with the neuroscience, tracks within a narrow range, consistent over time and across cultures.nnnMETHODSnPeer-reviewed publications reporting 24-hour urinary sodium excretion (UNaV) in a defined population that were not included in our 2009 publication were identified from the medical literature. These datasets were combined with those in our previous report of worldwide dietary sodium consumption.nnnRESULTSnThe new data included 129 surveys, representing 50,060 participants. The mean value and range of 24-hour UNaV in each of these datasets were within 1 SD of our previous estimate. The combined mean and normal range of sodium intake of the 129 datasets were nearly identical to that we previously reported (mean = 158.3±22.5 vs. 162.4±22.4 mmol/d). Merging the previous and new datasets (n = 190) yielded sodium consumption of 159.4±22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d).nnnCONCLUSIONSnHuman sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries. As documented here, this range is determined by physiologic needs rather than environmental factors. Future guidelines should be based on this biologically determined range.

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‐1α (IL‐1α 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‐1α 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‐1α 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 (Pu2003<u20030.02) 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.

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

Abstract: 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 μg/l (rs=0.53, p<0.0001). The prevalence of absent mobilizable body iron stores (serum ferritin <13 μg/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 μg/l and haemoglobin <129 g/l). Females: median ferritin values displayed a slight increase with age from 28 to 39 μg/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 μg/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.

Serum ferritin in children and adolescents. Results from population surveys in 1979 and 1986 comprising 1312 individuals

Abstract: Iron stores were assessed by measurement of serum ferritin in a population survey comprising 436 randomly selected urban Danish schoolchildren (219 boys, 217 girls) 7 to 17 years old. Median ferritin values were similar in boys and girls 7 to 13 years old, while 14‐ to 17‐year‐old boys had significantly higher values than girls of similar age (p< 0.0001). Boys had stable median ferritin values from 7 to 15 years of age, after which a significant rise was found from 16 to 17 years of age (p<0.01). Girls had unchanged median ferritin values from 7 to 11 years of age, after which a significant decrease was found from 12 to 17 years of age (p<0.01). The frequencies of low ferritin values < 16 μg/1 (indicating absent iron stores) were: Children 7 to 11 years, 1.0%. Boys 12 to 15 years, 4.5%; 16 to 17 years, 0%. Girls 12 to 15 years, 7.6%; 16 to 17 years, 16.7%. Ferritin levels in the reported 1986 survey were significantly higher than those obtained in a similar survey in the same area in 1979. The results indicate an overall increase in iron stores in Danish schoolchildren and adolescents during 1979–1986, possibly due to an increase in the consumption of meat, and in the use of vitamin‐mineral supplements containing iron.

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.

Public Policy and Dietary Sodium Restriction

children 6 years later. We speculate that the increase here largely reflects the detection of most of these problems in middle childhood, rather than at younger ages. We agree that obesity is a risk factor for a range of problems later in life, and treatments for obesity aim to prevent these problems rather than minimize active symptoms. However, there is evidence to support that treating obesity at earlier ages is needed to stave off the adverse effects later in life. This substantiates the argument for ongoing efforts to better prevent, detect, and treat childhood obesity in health care settings and in communities and schools. Although other methods of assessing obesity exist, BMI has had much study and is linked to adverse health outcomes in later childhood and adulthood. Furthermore, BMI is recommended and used for obesity assessment in clinical practice. We acknowledge that some parents reported these measurements, and our study conducted sensitivity analyses using objectively obtained data, which showed that parental report did not substantially change our findings.