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Biomedical subjects

Nils Milman

Publications and source records attributed to Nils Milman.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of lung transplanted patients with primary graft dysfunction.

OBJECTIVE: Primary graft dysfunction (PGD) causes significant mortality and morbidity after lung transplantation. The objectives of the study were to describe the clinical and histological sequelae of PGD. METHODS: Histology of all patients receiving single-lung transplantation 1999-2004 (n=181) was reviewed. PGD was defined as diffuse radiological infiltration of the lung allograft occurring within the first 72h postoperatively. RESULTS: One patient died intra-operatively. PGD was recorded in 63% (n=113) of 180 consecutive transplant recipients. Patients with PGD had a worse 90-day postoperative mortality (14% versus 3%, p=0.03) and 3-year survival (55% versus 77%, p=0.003). Freedom from bronchiolitis obliterans syndrome was similar in both groups. The maximal FEV(1) was significantly lower in patients with PGD, median 54% (quartiles 48-61%) predicted; compared to patients without PGD, median 59% (quartiles 54-69%) predicted (p=0.003). There was a significant linear trend in the decline of maximal FEV(1) with the presence and increasing severity of radiographic infiltrate (p=0.004). During follow-up, patients with PGD were more likely to demonstrate diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (p=0.009 and p=0.01, respectively). Histological findings of diffuse alveolar damage correlated closely with extent of radiological infiltration (p<0.0001). CONCLUSIONS: Transplant recipient survival, lung function, and histological findings of diffuse alveolar damage appear to be closely correlated with the appearance and severity of PGD.

Bronchiolitis Obliterans↗
PubMed2006

[Cardiac sarcoidosis].

The paper gives a review of the epidemiology, clinical manifestations, diagnosis, treatment and prognosis of cardiac sarcoidosis. Approximately 30% of patients with systemic sarcoidosis have granulomas in the myocardium, and 5% have clinical signs of cardiac affection. Cardiac manifestations comprise pericarditis, heart block, ventricular arrhythmias, valvular disease, ventricular aneurism, congestive heart failure and sudden cardiac death. Most frequent causes of death are sudden death and heart failure. Adequate treatment improves the prognosis of the disease.

Cardiomyopathies↗
PubMed2006

[Cardiac sarcoidosis--a difficult diagnosis. A report of 8 consecutive patients with arrhythmias and cardiomyopathy].

During the period 1984-2005, eight patients aged 25-57 years were treated for cardiac sarcoidosis. Diagnosis was obtained in three patients by endomyocardial biopsy, in three at heart transplantation (HTx) and in two at autopsy. Two patients had heart block, five ventricular arrhythmias and six dilated cardiomyopathy with congestive heart failure. Five patients died, one by sudden death, two of heart failure and two after HTx. Diagnosing cardiac sarcoidosis remains difficult, although MRI and PET scan have renewed the awareness of the disease.

Adult↗
PubMed2006

[Blau syndrome--a chronic granulomatous, genetic disease].

Blau syndrome is a rare hereditary granulomatous disease presenting in patients of young age with exanthema, granulomatous arthritis and uveitis. Genetic analysis has shown an autosomal dominant inheritance and a number of specific mutations on chromosome 16q in codon 334, of which the most predominant are R334W and R334Q. Blau syndrome exists in Caucasian, Asian and Afro-American families, and de novo mutations have been reported. The estimated minimum incidence in Denmark is 0.05 per 100,000 person-years. Blau syndrome has pathological, clinical and therapeutic features in common with sarcoidosis but rarely involves the lungs or other parenchymatous organs. Discrimination between Blau syndrome and early-onset sarcoidosis should rely on chromosome analysis.

Arthritis↗
PubMed2006

[Blau syndrome in monozygotic twins].

This case report describes Blau syndrome in monozygotic twins. The disease ran an identical course in both patients, starting with a maculopapulous exanthema at one year of age. Skin biopsies showed epithelioid cell granulomas with multinucleated giant cells. Shortly after arthritis and periarticular swelling developed and uveitis appeared at 8 years of age. Treatment consisted of prednisolone and methotrexate, and from 18 years of age of infliximab, with good effect. DNA analysis showed de novo R334W mutation in the CARD15 gene. The patients have now been followed for 19 years and are in good clinical condition.

Adolescent↗
PubMed2006

Rubidium content in autopsy liver tissue samples from Greenlandic Inuit and Danes measured by X-ray fluorescence spectrometry.

BACKGROUND: The biological function of rubidium (Rb) is unknown, but this alkali metal probably has a normal biologic role. OBJECTIVE: To measure the content of Rb in liver tissue samples from Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver samples from ethnic Danes. STUDY DESIGN: Observational, descriptive survey on environmental pathology. METHODS: The setting was related to forensic medicine and hospitalised care in Nuuk, Ilulissat and Copenhagen. Normal liver tissue was obtained at autopsy from 50 Greenlandic Inuit (27 men) with a median age of 61 years (range 23-83) and from 42 Danes (31 men) with a median age of 38 years (range 16-83). RESULTS: Liver Rb content in Inuit was not significantly different compared with Danes. There was no significant gender difference in liver Rb content either in Inuit or in Danes. The content of Rb given as median (5-95 percentile) was 0.1837mmol/kg dry liver (0.1041-0.3147) in Inuit, and 0.1965mmol/kg dry liver (0.0799-0.2815) in Danes (p=0.6). There was an inverse correlation between liver Rb content and age in Inuit (r(s)=-0.45, p=0.002) but not in Danes. Median hepatic Rb index (Rb content in micromol/kg dry weight divided by age in years) in Inuit was 3.05 and in Danes 4.21 (p=0.02). The correlations between liver Rb and liver potassium content were: Inuit r(s)=0.28, p=0.07; Danes r(s)=0.25, p=0.08; combined series r(s)=0.34, p=0.01. CONCLUSIONS: Inuit have liver Rb levels, which are quite similar to the levels found in Danes. In Inuit, liver Rb content appears to decrease with age.

Adolescent↗
PubMed2006

Iron prophylaxis in pregnancy--general or individual and in which dose?

Iron is mandatory for normal fetal development, including the brain. Iron deficiency may have deleterious effects for intelligence and behavioral development. It is important to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. Iron deficiency anemia during pregnancy is a risk factor for preterm delivery and low birth weight. In the Western countries there is no consensus on iron prophylaxis to pregnant women. An adequate iron balance during pregnancy implies body iron reserves of >or=500 mg at conception. The physiologic iron requirements in the second half of gestation cannot be fulfilled solely through dietary iron. Iron supplements during gestation consistently increase serum ferritin and hemoglobin and reduce the prevalence of iron deficiency anemia. Iron has a negative influence on absorption of other divalent metals and increases oxidative stress in pregnancy, for which reason minimum effective iron dose should be advised. From a physiologic point of view, individual iron prophylaxis according to serum ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are (1) ferritin>70 microg/l: no iron supplements; (2) ferritin 30-70 microg/l: 40 mg ferrous iron daily; and (3) ferritin<30 microg/l: 80-100 mg ferrous iron daily. In controlled studies, there are no documented side effects of iron supplements below 100 mg/day. Iron supplements should be taken at bedtime or between meals to ensure optimum absorption.

Anemia, Iron-Deficiency↗
PubMed2006

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 microg/l in pregnancy and <15 microg/l postpartum; IDA as serum ferritin <12 microg/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 70 microg/l. At 32 weeks, women with ferritin 30 microg/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 microg/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 microg/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 70 microg/l have no need for iron supplement.

Adult↗
PubMed2006

Iron and pregnancy--a delicate balance.

The review focuses on iron balance during pregnancy and postpartum in the Western affluent societies. Iron status and body iron can be monitored using serum ferritin, haemoglobin, serum soluble transferrin receptors (sTfR) and the sTfR/ferritin ratio. Requirements for absorbed iron increase during pregnancy from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester. Average requirement during the entire gestation is approximately 4.4 mg/day. Intestinal iron absorption increases during pregnancy, but women with ample body iron reserves have lower absorption than those with depleted reserves, so increased absorption is, in part, due to progressive iron depletion. Apparently, women do not change dietary habits when they become pregnant. Non-pregnant Scandinavian women have a median dietary iron intake of approximately 9 mg/day, i.e. more than 90% of the women have an intake below the recommended approximately 18 mg/day. Non-pregnant women have a low iron status, 42% have serum ferritin levels 70 microg/l corresponding to body iron of >or=500 mg. The association between high haemoglobin during gestation and a low birth weight of the newborns is caused by inappropriate haemodilution. In placebo-controlled studies on healthy pregnant women, there is no relationship between the women's haemoglobin and birth weight of the newborns and no increased frequency of preeclampsia in women taking iron supplements.

Anemia, Iron-Deficiency↗
PubMed2006

Cobalamin status during normal pregnancy and postpartum: a longitudinal study comprising 406 Danish women.

OBJECTIVES: To assess cobalamin (vitamin B(12)) status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study was performed in 1995-1996. It comprised 406 healthy, pregnant Danish Caucasian women, living in Copenhagen County. Cobalamin status, i.e. plasma (P-) cobalamin, P-methylmalonic acid and P-homocysteine was measured at 18, 32 and 39 wk gestation and 8 wk postpartum during lactation. RESULTS: P-cobalamin showed a gradual, significant decline during pregnancy (P < 0.0001) followed by a significant increase postpartum (P < 0.0001); at 18, 32, 39 wk gestation and 8 wk postpartum median values were 225, 172, 161 and 319 pmol/L, respectively. P-methylmalonic displayed a gradual, significant increase during pregnancy as well as postpartum (P < 0.001) with median values of 0.11, 0.13, 0.14, and 0.16 micromol/L, respectively. P-homocysteine demonstrated a significant increase during pregnancy and postpartum (P < 0.001). The frequency of P-cobalamin values <150 pmol/L increased during pregnancy from 15% at 18 wk to 43% at 39 wk gestation and subsequently declined to 3% postpartum. CONCLUSION: Low cobalamin status may occur among pregnant women, especially in late pregnancy. The recommendations for periconceptional vitamin B(12) supplementation should be reconsidered.

Adult↗
PubMed2006

[Treatment of severe sarcoidosis using TNF-alpha-inhibitor (infliximab)].

Some patients with severe sarcoidosis are resistant to conventional treatment with corticosteroids and cytostatics. We describe a 29-year-old man with histologically verified sarcoidosis and persistent, pronounced enlargement of the peripheral lymph nodes, resistant to treatment with prednisolone and methotrexate. Following treatment with TNF-alpha-inhibitor (infliximab 3 mg/kg body weight), the lymph nodes regressed to normal size and the patient improved clinically. The patient had a total of four infliximab infusions, and the effect has persisted for more than two years.

Adult↗
PubMed2006

Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: a longitudinal study comprising 404 Danish women.

OBJECTIVE: To assess folate and homocysteine status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study, performed in 1995-1996, comprised 404 healthy pregnant Danish Caucasian women residential in Copenhagen County. Women taking folic acid tablets or vitamin B12 injections were not included. Dietary multivitamin supplements containing folic acid 100 microg or vitamin B12 1 microg, taken by 34%, were discontinued at inclusion. Participants had normal renal function. Folate status [erythrocyte (Ery-) folate, plasma (P-) folate, P-homocysteine] was measured at 18, 32 and 39 wk of gestation and 8 wk postpartum when the women were lactating. RESULTS: Through 18, 32 and 39 wk of gestation and postpartum, P-folate demonstrated a significant fall: median values were 14.4, 10.2, 9.3 and 8.9 nmol/L, respectively (P < 0.0001). The prevalence of low P-folate <6 nmol/L increased during pregnancy from 0.7% to 19.0% postpartum (P < 0.0001). Ery-folate displayed a similar, significant fall: median value was 0.84, 0.75, 0.65 and 0.55 micromol/L, respectively (P < 0.0001). The prevalence of low Ery-folate <0.40 micromol/L increased during pregnancy from 0.5% to 17.2% postpartum (P < 0.0001). P-homocysteine demonstrated a significant increase: median value was 6.4, 7.0, 7.7 and 10.8 micromol/L, respectively (P < 0.0001). The prevalence of P-homocysteine >13 micromol/L increased during pregnancy from 0.7% to 20.8% postpartum (P < 0.0001). The prevalence of low folate status (defined as P-folate <6 nmol/L and P-homocysteine >13 micromol/L) was 0%, 0%, 1.2%, and 8.4% at 18, 32 and 39 wk of gestation and 8 wk postpartum, respectively. CONCLUSION: Low folate status occurs among Danish pregnant women, especially in late pregnancy and postpartum during lactation. Despite new guidelines for folic acid supplement since 1997, only 13% of pregnant women followed the guidelines in 2003. The official recommendations for periconceptional folic acid supplement should be reconsidered and reinforced.

Adult↗
PubMed2006

CARD15 single nucleotide polymorphisms 8, 12 and 13 are not increased in ethnic Danes with sarcoidosis.

BACKGROUND: Mutations of the caspase-activating recruitment domain 15 (CARD15) gene on chromosome 16 are associated with chronic inflammatory granulomatous bowel disease (Crohn's disease). Sarcoidosis is a systemic granulomatous disease with unknown etiology, which shares histological features with Crohn's disease. OBJECTIVES: To evaluate whether ethnic Danes with sarcoidosis have an increased frequency of CARD15 mutations compared to healthy control subjects. METHODS: Genotyping for CARD15 mutations R702W, G908R, and L1007fsinsC, also designated single nucleotide polymorphism (SNP) SNP8, SNP12 and SNP13, respectively, were performed by capillary electrophoresis single-strand confirmation polymorphism in 53 patients with histologically verified sarcoidosis and in 103 healthy controls. RESULTS: The frequencies of CARD15 mutations in sarcoidosis patients were: SNP8, 4/106 chromosomes (3.8%); SNP12, 2/106 chromosomes (1.9%); SNP13, 2/106 chromosomes (1.9%); SNP8+SNP12+SNP13, 8/106 chromosomes (7.6%). All 8 patients were heterozygous. The frequencies in controls were: SNP8, 9/206 chromosomes (4.4%); SNP12, 2/206 chromosomes (1.0%); SNP13, 4/206 chromosomes (1.9%); SNP8+SNP12+SNP13, 15/206 chromosomes (7.3%). All controls were heterozygous. The differences were not statistically significant (p>0.05). Furthermore, the course of disease was not significantly different in the 8 patients with CARD15 mutations and the 45 patients without mutations. CONCLUSION: The frequency of CARD15 mutations is not increased in ethnic Danish patients with sarcoidosis, and heterozygosity for such mutations apparently has no influence on the course of disease.

Adult↗
PubMed2006

The incidence of acute cellular rejection after lung transplantation: a comparative study of anti-thymocyte globulin and daclizumab.

OBJECTIVE: This study examined the effects of anti-thymocyte globulin (ATG) and daclizumab immunosuppressive induction therapy on the frequency and severity of acute cellular rejection in lung transplantation patients. METHOD: A retrospective analysis was conducted of 335 lung transplantation patients from a single center in the period 1992 to 2003. Patients completed standard ATG (Merieux, 2.5 mg/kg/day, or ATGAM, 12.5 mg/kg/day, for 3 consecutive days) (n = 151) or daclizumab (5 fortnightly treatments at a dose of 1 mg/kg) (n = 151) induction therapy. End points included acute cellular rejection requiring treatment (> or = A2), and moderate/severe acute cellular rejection (A3/A4). RESULTS: The percentage of patients free of rejection requiring treatment (< A2) was 32% at 3 months and 26% at 2 years after transplantation in the ATG group and 9% and 0%, respectively, in the daclizumab group (p < 0.0001). Compared with the ATG group, a significantly higher proportion of patients in the daclizumab group experienced 3 or more episodes of acute cellular rejection > or = A2 during the first 3 months (p < 0.0001) and the entire 2-year follow-up (p < 0.0001). The daclizumab group also experienced more moderate/severe acute cellular rejection episodes compared with the ATG group during the first 3 months (p = 0.005). Cox regression analysis demonstrated ATG induction therapy was independently associated with a significantly longer duration of freedom from acute cellular rejection requiring treatment (> or = A2) (p < 0.001). CONCLUSION: After lung transplantation, ATG induction appears to be superior to daclizumab induction in the reduction in the incidence and severity of acute cellular rejection.

Antibodies, Monoclonal↗
PubMed2006

Cytomegalovirus infection in lung transplant patients: the role of prophylaxis and recipient-donor serotype matching.

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in lung transplant recipients. We investigated the incidence of CMV infection in relation to CMV prophylaxis, and recipient-donor CMV serotype, in a cohort of 250 consecutive lung transplant recipients. All patients received 3 months CMV prophylaxis with acyclovir (n = 67) or gancyclovir (n = 183). Recipient-donor CMV serotype matching was performed in patients receiving acyclovir: R+/D+(n = 38), R+/D-(n = 10), R-/D+(n = 1), R- /D-(n = 16), unknown (n = 2). Recipient-donor CMV serotype matching was not performed in patients receiving gancyclovir: R+/D+(n = 71), R+/D-(n = 42), R-/D+(n = 38), R-/D-(n = 31), unknown (n = 1). The overall incidence of CMV infection was 51% (n = 34) in the acyclovir group, and 42% (n = 77) in the gancyclovir group (p = 0.14). During the first 9 months after transplantation, the rate of CMV infection was higher in the acyclovir group (42%) compared with the gancyclovir group (30%) (p = 0.005). Multivariate analysis demonstrated the incidence of CMV infection during the first 9 months was higher for acyclovir prophylaxis (p<0.001) and R-/D+ serostatus (p<0.001) and lower with R-/D- serostatus (p = 0.02). In conclusion, gancyclovir significantly delays the onset of first CMV infection among lung transplant patients. CMV surveillance and choice of prophylaxis may be modified according to donor-recipient CMV serotype.

Acyclovir↗
PubMed2006

Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation.

Blau syndrome is a hereditary granulomatous disease caused by mutations in the CARD15 gene that is diagnosed in children of young age with exanthema/erythema, arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in Danish Caucasian monozygotic male twins, exhibiting a heterozygous de novo R334W mutation in codon 334 of CARD15. The patients were initially diagnosed as having sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started at 1 year of age, and were followed by uveitis at 7-10 years of age. There was no involvement of the lungs or other organs. An initial course of standard antituberculous treatment had no effect on the symptoms. Hydroxychloroquine and cyclosporine A were also ineffective, and the latter caused impaired renal function. Partial symptomatic relief was obtained with prednisolone and increased benefit was observed in combination with methotrexate. Subsequent introduction of the TNF-alpha inhibitor eternacept did not discernibly benefit the clinical condition, but was associated with recurrent infections. In contrast, a trial of infliximab therapy demonstrated clinical efficacy and eliminated all symptoms, restoring a high quality of life. At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features in common with sarcoidosis, but rarely involves the lungs or other parenchymatous organs. In children, discrimination between early onset sarcoidosis and Blau syndrome should include a CARD15 mutation analysis.

Adult↗
PubMed2006

Side effects of oral iron prophylaxis in pregnancy--myth or reality?

BACKGROUND: It is a common belief among women that iron compounds have unpleasant gastrointestinal side effects. OBJECTIVE: To assess the gastrointestinal side effects of iron prophylaxis in pregnancy. METHODS: A randomized, double-blind study comprising 404 healthy pregnant women allocated to four groups taking ferrous iron supplement (as fumarate) in doses of 20 (n = 99), 40 (n = 100), 60 (n = 102) and 80 mg (n = 103) daily from 18 weeks of gestation to delivery. Iron supplement was predominantly taken at bedtime. Gastrointestinal symptoms (nausea, vomiting, epigastric pain, eructation, pyrosis, meteorism, borborygmi, colic pain, flatulence, constipation, thin feces, diarrhea), black feces, and use of laxatives were recorded by interview at 18, 32 and 39 weeks of gestation. RESULTS: The frequencies of gastrointestinal symptoms were not significantly different in the four iron supplement groups either at inclusion or at 32 and 39 weeks of gestation and thus not related to the iron dose. CONCLUSION: This study shows that a supplement of 20-80 mg ferrous iron (as fumarate), taken between meals, has no clinically significant gastrointestinal side effects. The implementation of iron prophylaxis to pregnant women should not be compromised by undue concern of non-existing side effects.

Administration, Oral↗