Childhood sarcoidosis in Denmark 1979-1994: incidence, clinical features and laboratory results at presentation in 48 children

Aim: To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979-1994. Methods: Patients (n = 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were ≤15 y of age. The diagnosis of sarcoidosis was reconfirmed in 48/81 (59%) patients. In 35/48 (73%) patients, diagnosis was verified by histology, and in 13 it was substantiated by paraclinical/clinical findings. Results: The series comprised 26 boys and 22 girls (male/female ratio 1.18). Median age at diagnosis was 13 y (range 0.7-15). In 1979-1994 the incidence was 0.29 per 100 000 person-years ≤15 y of age. The incidence was 0.06 in children ≤4 y of age and increased gradually with age to 1.02 in children aged 14-15 y. General malaise, fever, weight loss, abdominal discomfort, respiratory symptoms, lymphadenopathy and central nervous system symptoms were common; 31% of patients had erythema nodosum, 12.5% sarcoid skin lesions, 25% uveitis/iridocyclitis and 4.2% sarcoid arthritis. Chest X-rays were normal (stage 0) in 10% of patients, and showed pulmonary infiltrates stage I in 71%, stage II in 8.3% and stage III in 8.3%. Lung function tests were examined in 13 patients: 50% had decreased FEV ₁ and vital capacity, 80% decreased D _L CO. Haemoglobin values were normal. Some patients had mild leukopenia, some moderate leukocytosis and a few had moderate eosinophilia. Erythrocyte sedimentation rate was elevated in 40% of the patients. Plasma calcium was elevated in 30% of the patients; 4 patients had severe hypercalcaemia and elevated plasma creatinine, and 1 patient had nephrocalcinosis. Serum angiotensin-converting enzyme was elevated in 55% of the patients. Liver function tests were normal with no sarcoid hepatitis. Urinary examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria.

Conclusion: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features that are different from the appearance of those in older children and often constitute a diagnostic challenge. In older children, the clinical appearance has many features in common with the presentation in adults.     

Sarcoidosis in Denmark 1980-1994. A registry-based incidence study comprising 5536 patients

BACKGROUND AND AIM: To evaluate the incidence of sarcoidosis in Denmark 1980-1994. METHODS: Patients with a diagnosis of sarcoidosis were identified from the Danish National Patient Registry. The file contained information about the year in which the diagnosis was reported, gender, age, and residential county. RESULTS: 5536 persons (2816 men) with sarcoidosis were registered. Median age in men was 38 years, in women 45 years. The male/female incidence ratio was 1.06. The incidence (per 100,000 person years) declined gradually from 8.1 in 1980-1984 to 6.4 in 1990-1994. The overall incidence in 1980-1994 was 7.2. Incidence rates 1980-1994 increased from eastern to western parts of Denmark: Zealand 5.7, Funen 6.8, and Jutland 8.4. The peak incidence in men occurred at 30-34 years of age (14.8). Women displayed two similar peak incidences at 25-29 years of age (10.5) and at 65-69 years of age (11.0). CONCLUSION: Incidence rates in the present study are lower compared with previous mass-screening surveys showing an incidence rate of 13.8 (in persons examined). Peak incidences occurred at higher ages in both men and women. Previous surveys showed peak incidences at 20-25 years in men and at 25-30 years and 50 years in women. The overall incidence of sarcoidosis in Denmark ranges from 7-10 per 100,000 person years. With 5,500,000 residents, the expected number of new cases of sarcoidosis in Denmark is between 385 and 550 per year.     

Iron status markers in 224 indigenous Greenlanders: influence of age, residence and traditional foods

OBJECTIVE: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods. Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic individuals (109 men) aged 19-82 yr. The participants were residents in the capital Nuuk (n=73) with a predominantly Western style of living, the town Ilulissat (n=60) with a mixture of Western and Greenlandic style of living, and the small town Uummannaq (n=91) with a predominantly Greenlandic style of living. Consumption of traditional foods was assessed by questionnaire. RESULTS: Intake of traditional foods was more prevalent among elderly than among young individuals and more frequent in Uummannaq than in Ilulissat and Nuuk. Ferritin levels were higher in men than in women (p<0.0001). Median ferritin levels were lowest in Nuuk (men, 92 microg/L; women, 40 microg/L), higher in Ilulissat (men, 104 microg/L; women, 69 microg/L) and in Uummannaq (men, 118 microg/L; women, 46 microg/L) (p<0.001). The prevalence of iron load (ferritin >200 microg/L) was lowest in Nuuk (men: 13.8%, women: 2.3%) intermediate in Ilulissat (men, 11.1%; women, 9.1%) and highest in Uummannaq (men, 32.1%; women, 21.1%). The prevalence of iron depletion (ferritin <16 microg/L) was high in Nuuk (men, 0%; women, 20.5%), and lower in Ilulissat (men, 3.7%; women, 6.1%) and in Uummannaq (men, 0%; women, 10.5%). The prevalence of iron deficiency anaemia (ferritin <13 microg/L and Hb <5th percentile for iron-replete men and women) was 0.92% in men and 0.87% in women. Correlations between age and ferritin were lowest in Nuuk (men, r(s)=0.26, p=0.2; women, r(s)=0.50, p=0.001) intermediary in Ilulissat (men, r(s)=0.37, p=0.06; women, r(s)=0.73, p<0.0001) and highest in Uummannaq (men, r(s)=0.59, p<0.0001; women, rs=0.74, p<0.0001). Intake of traditional foods was correlated with ferritin in men (r(s)=0.29, p=0.01) and women (r(s)=0.40, p<0.0001). CONCLUSION: The observed differences in estimated body iron stores in Greenlanders from the three residential areas can be explained by differences in the dietary intake of haem iron.     

Erythropoiesis: Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Erythropoiesis: Short Report: Translation of Analysis Results between Serum Ferritin Assays, Ferritin RIA AmershamTM and Abbott AxSYMTM Ferritin

The serum ferritin assays, Ferritin RIA Amersham(TM) and Abbott AxSYM(TM) Ferritin were compared in order to translate values from one assay to the other. Serum ferritin was analysed with both assays in 102 samples. Logarithmic transformation of the results was performed in order to stabilize the variance. The relationship between the untransformed values was most exactly expressed by a proportionality: AxSYM Ferritin = 0.873 * RIA Ferritin. Due to this proportionality, the numerical difference between the assays increases with the ferritin concentration, although the percentage difference between the assays remains constant.     

Iron status in 268 Danish women aged 18–30 years: influence of menstruation, contraceptive method, and iron supplementation

 The aim of the present study was to evaluate the influence of menstruation, method of contraception, and iron supplementation on iron status in young Danish women, and to assess whether iron deficiency could be predicted from the pattern of menstruation. Iron status was examined by measuring serum (S-) ferritin and hemoglobin (Hb) in 268 randomly selected, healthy, menstruating, nonpregnant Danish women aged 18–30 years. Iron deficiency (S-ferritin <16 μg/l) was observed in 9.7% of the women, iron deficiency anemia (S-ferritin <13 μg/l and Hb <121 g/l) in 2.2%. Iron supplementation, predominantly as vitamin-mineral tablets containing 14–20 mg of ferrous iron was used by 35.1%. The median serum ferritin was similar in non-iron users and in iron users, whereas the prevalence of iron deficiency was 12.6% in nonusers vs. 4.3% in users, the prevalence of iron deficiency anemia 3.4% in nonusers vs. 0% in users (p=0.17) In non-iron-supplemented women, S-ferritin levels were inversely correlated with the duration of menstrual bleeding (r _s=–0.25, p<0.001) and with the women's assessment of the intensity of menstrual bleeding (r _s=–0.27, p<0.001), whereas no such correlations were found in iron-supplemented women. The results demonstrate that even moderate daily doses of ferrous iron can influence iron status in women with small iron stores. Women using hormonal contraceptives had menstrual bleeding of significantly shorter duration than those using intrauterine devices (IUD) or other methods. There was a high prevalence of small and absent body iron stores in young women, suggesting that preventive measures should be focused on those women whose menstruation lasts 5 days or longer, who have menstrual bleeding of strong intensity, who use an IUD without gestagen, and who are blood donors. Received: December 10, 1998 / Accepted: May 22, 1998     

Effects of F/G-actin ratio and actin turn-over rate on NADPH oxidase activity in microglia

Background

Egg white must provide nutrients and protection to the developing avian embryo. One way in which this is achieved is an arsenal of antimicrobial proteins and peptides which are essentially extensions of the innate immune system. Gallin is a recently identified member of a family of peptides that are found in egg white. The function of this peptide family has not been identified and they are potentially antimicrobial.

Results

We have confirmed that there are at least 3 forms of the gallin gene in the chicken genome in 3 separate lines of chicken, all the forms are expressed in the tubular cells of the magnum region of the oviduct, consistent with its presence in egg white. mRNA expression levels are in the order 10,000 times greater in the magnum than the shell gland. The conservation between the multiple forms of gallin in the chicken genome compared with the conservation between gallin and other avian gallin like peptides, suggests that the gene duplication has occurred relatively recently in the chicken lineage. The gallin peptide family contains a six cysteine motif (C-X₅-C-X₃-C-X₁₁-C-X₃-C-C) found in all defensins, and is most closely related to avian beta-defensins, although the cysteine spacing differs. Further support for the classification comes from the presence of a glycine at position 10 in the 41 amino acid peptide. Recombinant gallin inhibited the growth of Escherischia coli (E. coli) at a concentration of 0.25 μM confirming it as part of the antimicrobial innate immune system in avian species.

Conclusions

The relatively recent evolution of multiple forms of a member of a new defensin related group of peptides that we have termed ovodefensins, may be an adaptation to increase expression or the first steps in divergent evolution of the gene in chickens. The potent antimicrobial activity of the peptide against E. coli increases our understanding of the antimicrobial strategies of the avian innate immune system particularly those of the egg white and the evolution of the defensin family. The potential of this peptide and others in the family can now be investigated in a number of novel antimicrobial roles.     

Short Report: Translation of Analysis Results between Serum Ferritin Assays,Ferritin RIA Amersham™ and Abbott AxSYM™ Ferritin

The serum ferritin assays, Ferritin RIA Amersham? and Abbott AxSYM? Ferritin were compared in order to translate values from one assay to the other. Serum ferritin was analysed with both assays in 102 samples. Logarithmic transformation of the results was performed in order to stabilize the variance. The relationship between the untransformed values was most exactly expressed by a proportionality: AxSYM Ferritin = 0.873 * RIA Ferritin. Due to this proportionality, the numerical difference between the assays increases with the ferritin concentration, although the percentage difference between the assays remains constant.     

Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Body iron and individual iron prophylaxis in pregnancy—should the iron dose be adjusted according to serum ferritin?

This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12 μg/l in pregnancy and <15 μg/l postpartum; IDA as serum ferritin <12 μg/l and haemoglobin <5th percentile in iron-replete pregnant women. Women in the iron supplement groups were stratified according to serum ferritin levels at inclusion; 50.7% had ferritin ≤30 μg/l, 37.7% ferritin 30–70 μg/l and 11.6% ferritin >70 μg/l. At 32 weeks, women with ferritin ≤30 μg/l had an ID frequency of: 20-mg group 54.1%, 40 mg 29.7%, 60 mg 24.4%, 80 mg 20.6% (p<0.001); women with ferritin >30 μg/l had an ID frequency of: 20-mg group 20.0%, 40 mg 13.9%, 60 mg 5.7%, 80 mg 5.1% (p<0.001). Women with ferritin >70 μg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40 mg and 0% in group 60 and 80 mg. IDA: At 32 weeks, women with ferritin ≤30 μg/l had an IDA frequency of: 20-mg group 2.7%, 40 mg 2.7%, 60 and 80 mg 0%; none of the women with ferritin >30 μg/l displayed IDA. Body iron at 18 weeks was 10.4 mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20 mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3 mg/kg in the 20-mg group and 10.5 mg/kg in the 40-, 60- and 80-mg groups. This study gives an estimate of iron dosage in individual iron prophylaxis adjusted to serum ferritin levels in early pregnancy. In the prevention of ID, we suggest 80–100 mg ferrous iron/day to women having ferritin ≤30 μg/l and 40 mg ferrous iron/day to women having ferritin 31–70 μg/l. In the prevention of IDA, we suggest 40 mg ferrous iron/day to women having ferritin ≤70 μg/l. Women with ferritin >70 μg/l have no need for iron supplement.