[Diagnosis of pulmonary fibrosis].
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Biomedical subjects
Publications and source records attributed to N Milman.
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Transferrin (TF) subtypes were determined by isoelectric focusing in 51 unrelated Danish patients with hereditary haemochromatosis (HH) and in 847 normal subjects. The following TF phenotype frequencies were observed in HH patients and controls, respectively: TF*C1, 70.6% vs. 58.8%; TF*C2, 5.9% vs. 2.4%; TF*C3, 0% vs. 0.4%; TF*C1-2, 11.8% vs. 24.7%; TF*C1-3, 5.9% vs. 9.7%; TF*C2-3, 3.9% vs. 2.2%; TF*B-C1, 2.0% vs. 1.5%; TF*B-C2, 0% vs. 0.4%. None of these differences were statistically significant. There was no relationship between the TF subtypes and the clinical or paraclinical expression of disease in HH patients.
Iron status was assessed by measuring serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 1359 nonpregnant Danish women, in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Median age for menarche was 14 years, for menopause (artificial and natural) 48 years. Premenopausal women had lower S-ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l; p less than 0.0001). Of the premenopausal women, 17.7% had S-ferritin less than 15 micrograms/l (i.e., depleted iron stores), and 23.1% S-ferritin of 15-30 micrograms/l (i.e., small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Hb values in premenopausal women were mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) vs. 140 +/- 10 g/l (8.7 +/- 0.6 mmol/l) in postmenopausal women (p less than 0.0001); 4.1% of pre- and 3.3% of postmenopausal women had values less than 121 g/l (7.5 mmol/l). Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was found in 2.6% of pre- and 0.36% of postmenopausal women. Premenopausal multipara had lower S-ferritin than nulli- and unipara (p less than 0.04). The use of oral contraceptives had a marked influence on iron stores; premenopausal women taking the pill had higher S-ferritin and a lower frequency of depleted iron reserves than nonusers (p less than 0.01). Postmenopausal estrogen treatment had no influence on S-ferritin or Hb.
Iron status, including serum (S-)ferritin and hemoglobin (Hb), was assessed in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years. S-ferritin levels were similar in 30- and 40-year-old women; they displayed a significant increase in 50-year-old women and a further significant increase in 60-year-old women. In the 30- and 40-year-old women, median S-ferritin was 38 micrograms/l, 5-95 percentile 6-135 micrograms/l; 17.2% had values less than 15 micrograms/l (i.e., depleted iron stores), 22.7% values from 15 to 30 micrograms/l (i.e., small iron stores), and 60.1% values greater than 30 micrograms/l (i.e., replete iron stores). In the 50-year-old women, median S-ferritin was 54 micrograms/l, 5-95 percentile 10-164 micrograms/l; 10.3% had values less than 15 micrograms/l, 16.5% values from 15 to 30 micrograms/l, and 73.2% values greater than 30 micrograms/l. For the 60-year-old women, median S-ferritin was 84 micrograms/l, 5-95 percentile 25-249 micrograms/l; 1.6% had values less than 15 micrograms/l, 8.6% values from 15 to 30 micrograms/l, and 89.8% values greater than 30 micrograms/l. Blood donors (n = 180) had lower S-ferritin than nondonors in all age-groups (p less than 0.001). In the entire series, Hb levels were similar in 30- and 40-year-old women, median 137 milligrams (8.5 mmol/l), 5-95 percentile 121-152 milligrams (7.5-9.4 mmol/l), and higher in 50- and 60-year-old women, median 140 milligrams (8.7 mmol/l), 5-95 percentile 123-158 milligrams (7.6-9.8 mmol/l) (p less than 0.0001). Hb values less than 121 milligrams (7.5 mmol/l) were observed in 3.8% of the women. Women with S-ferritin less than 15 micrograms/l (n = 161) had lower Hb, median 134 milligrams (8.3 mmol/l), than those with S-ferritin greater than or equal to 15 micrograms/l, median 139 milligrams (8.6 mmol/l) (p less than 0.001). Iron deficiency anemia (S-ferritin less than 15 micrograms/l and Hb less than 121 milligrams) was seen in 2.3% of 30- and 40-year-old women, and in 1.1% of 50- and 60-year-old women.
The major extracellular enzyme of Legionella pneumophila, a metalloprotease, has been proposed as a pathogenic factor in Legionnaires' disease due to its cytotoxic, tissue-destructive, and phagocyte-inhibitory properties. The relevance of these activities depends on the production of the protease during infection, i.e. by L. pneumophila multiplying intracellularly. In this study, L. pneumophila was demonstrated to produce protease in guinea-pig and human alveolar macrophages infected in vitro. After 24 h infection, approximately 0.1 to 0.2 micrograms of protease per 10(6) bacteria was measured by ELISA in culture supernatants and lysates of the infected cells, whereas no protease could be detected immediately after infection. Immunogold labelling using anti-protease antibody showed the enzyme to be located within phagosomes and distributed throughout the macrophages. Recent observations have shown that this protease could modify host defence mechanisms through inhibition of bacterial killing by neutrophils and monocytes. The intracellular production of the enzyme in infected macrophages demonstrated here further supports a role for the protease in the pathogenesis of Legionnaires' disease.
Bronchiolo-alveolar carcinoma is usually localized to the terminal bronchioles and alveoli, and may present on chest X-ray as interstitial pulmonary disease with diffuse reticulonodular infiltrates. The cytological diagnosis is often difficult to obtain. This case demonstrates that bronchoalveolar lavage can be useful in the diagnostic evaluation of this type of malignancy, in conjunction with transbronchial lung biopsy.
HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc less than 0.001); B7: 33.1% vs. 15.6% (Pc less than 0.001); B14: 6.9% vs. 3.0% (Pc greater than 0.05); B38: 5% vs. 0.9% (Pc greater than 0.05); B47: 4.0% vs. 0.4% (Pc greater than 0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc less than 0.001); A3,B7: 25.6% vs. 6.6% (Pc = 0.001); A3,B14: 3.4% vs. 0.6% (Pc greater than 0.05); A3,B47: 6.9% vs. 0.2% (Pc greater than 0.05). The major IH marker HLA-A3 was found in 56% of the haplotypes. The patterns of HLA-alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3,B14 dominated.
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Superoxide anion release (O2-) after stimulation with phorbol myristate acetate was measured in alveolar macrophages (AM) obtained by bronchoalveolar lavage and in blood monocytes from 47 patients with diffuse interstitial lung disease: idiopathic pulmonary fibrosis (N = 15), hypersensitivity pneumonitis (N = 7), pneumoconiosis (N = 6) and sarcoidosis (N = 19). Differential cell counts demonstrated a lymphocyte predominance in patients with hypersensitivity pneumonitis (HP) and sarcoidosis while the other groups had neutrophil predominance. No correlation between O2- activity in alveolar macrophages (AM) or blood monocytes (BM) compared to lung function (VC and diffusing capacity) could be demonstrated. Smoking pneumoconiotics had significantly decreased BM O2- release (1.25 +/- 0.25 (SEM) nmol/min/10(6) cells) and significantly increased AM/BM O2- ratios (2.04 +/- 0.26) compared to smokers with idiopathic pulmonary fibrosis (IPF) who had the following mean values: BM O2- release = 2.58 +/- 0.25 and AM/BM O2- ratio = 0.86 +/- 0.23. When matched for sex and smoking, a significantly increased AM/BM O2- ratio was seen among patients with HP (2.19 +/- 0.98) in comparison with patients who had sarcoidosis (0.40 +/- 0.18). Patients with either HP or pneumoconiosis had generally elevated AM O2- release and reduced BM O2- release. These results suggest that environmentally related interstitial lung disorders (HP and pneumoconiosis) may be associated with elevated AM O2- release relative to BM O2- release in comparison to non-environmentally related disorders (IPF or sarcoidosis).
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Serum (S-) ferritin was analyzed in 67 Greenlandic Inuit hunters from Thule (Qaanaaq), 35 males and 32 females with a median age of 39 years (range 17-77). S-ferritin was higher in males, median 211 micrograms/l (range 30-1040), than in females, median 87 micrograms/l (range 33-794) (p less than 0.01). None of the subjects had S-ferritin less than or equal to 20 micrograms/l (i.e. depleted iron stores); 5 of the 48 subjects less than or equal to 50 years old had S-ferritin 21-40 micrograms/l (i.e. small iron stores). All 19 subjects greater than 50 years old had S-ferritin greater than 40 micrograms/l (i.e. replete iron stores) and 8 showed values greater than 300 micrograms/l (i.e. increased iron stores). S-ferritin levels increased with the percent energy intake from traditional native hunter food (rs = 0.26, p less than 0.05). Inuit had higher S-ferritin than Danish Caucasian subjects. In Inuit of both sexes, S-ferritin displayed a correlation to age (rs = 0.63, p less than 0.0001 in the entire series), indicating gradually increasing S-ferritin levels during lifetime, without the plateaus seen in Caucasians. These findings suggest continued accumulation of iron reserves in elderly Inuit, due to consumption of large quantities of iron rich meat from marine mammals and/or genetic differences in the regulatory mechanisms for body iron stores.
Gaucher's disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase with accumulation of glucocerebroside in the reticuloendothelial system. Affection of the lungs by this disease is extremely rare. When Gaucher cells infiltrate the lung, fibrosis may result. We describe a case with adult type Gaucher's disease who, besides affection of liver, spleen and bone marrow, had severe pulmonary involvement with extensive interstitial fibrosis, increased pulmonary vascular resistance, and pronounced reduction in diffusion capacity.
Fourty-three patients (28 males, 15 females, median age 50 years) with iatrogenic pneumothorax following invasive diagnostic procedures (percutaneous transthoracic fine needle aspiration biopsy 26, fiberoptic transbronchial biopsy 14, pleurocentesis 3), were treated with small calibre thoracic tube drainage. The tube consisted of a teflon catheter, 160 mm long, 2 mm in outer diameter which was inserted into the second intercostal space in the mid-clavicular line in local analgesia. Pneumothorax was evacuated by intermittent aspiration with a syringe in 16 patients. In the remaining 27 patients the catheter was connected to a one way flutter valve. Treatment was uncomplicated in all patients and successful in 41 (95%) patients, while two required a large calibre chest tube on account of persistent leakage. The median drainage time was 48 hours. Small calibre thoracic tube with a one way flutter valve is convenient for treatment of iatrogenic pneumothorax, being less traumatic and less expensive than conventional thoracic tube drainage.
Fiberoptic bronchoscopy was performed in local anaesthesia with lidocaine in 16 patients. Serum concentrations of lidocaine and its active metabolite monoethylglycinexylidide (MEGX) were measured at regular intervals up to 120 min. after administration. Lidocaine was administered as aerosol in the upper respiratory tract and as solution in the bronchial tree. The total lidocaine dose was 243-608 mg (2.4-8.0 mg/kg); 163-508 mg (1.6-6.6 mg/kg) was given as aerosol, and 60-180 mg (0.8-2.5 mg/kg) as solution. The highest median S-lidocaine concentration, 10.5 mumol/l, was measured 20 min. after administration. None of the patients had toxic S-lidocaine levels (greater than 26 mumol/l) and no adverse effects were observed. The highest median S-MEGX concentration, 1.7 mumol/l, was measured 120 min. after administration. The highest individual S-MEGX was 3.5 mumol/l. The highest, although insignificant, correlation coefficients were found between lidocaine dose expressed in mg/kg body weight and S-lidocaine and S-MEGX.
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The clinical appearance of sarcoidosis and the changes seen on x-ray of the thorax are often typical. However, several other conditions may present the same symptoms and identical x-ray findings. The present case report emphasizes the importance of an invasive approach and of histological investigation in patients in whom carcoidosis is suspected. For almost one year, a man aged 29 years was considered to be suffering from sarcoidosis on account of the clinical symptoms and bilateral hilar adenitis on x-ray op the thorax. He was treated with steroid for several months with clinical and radiological response. After the illness has lasted for one year, bronchoscopy was performed and bronchial biopsies revealed the diagnosis of malignant lymphoma.
The general impact of blood donation on iron status was studied in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal; 180 (13%) were blood donors. Iron stores were assessed by serum (S)-ferritin and hemoglobin (Hb). Hb levels were not significantly different in donors: mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) compared with nondonors, 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l). Values less than 121 g/l (7.5 mmol/l) were observed in 3.3% of donors vs 3.8% of nondonors. Correlations between S-ferritin and Hb were without practical relevance: rs = 0.29, p less than 0.0001 in donors vs rs = 0.22, p less than 0.0001 in nondonors. Blood donation had a profound influence on iron status, especially in the premenopausal women population. Donors had lower S-ferritin than nondonors in all age-groups and in pre- and postmenopausal groups (p less than 0.001 in all groups). Premenopausal donors had a median S-ferritin of 31 micrograms/l vs 39 micrograms/l in nondonors, postmenopausal donors of 47 micrograms/l vs 72 micrograms/l in nondonors. S-ferritin values less than 15 micrograms/l (i.e., depleted iron stores) were observed in 31.7% of premenopausal donors vs 15.2% of nondonors, and in 7.0% of postmenopausal donors vs 2.9% of nondonors. Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was seen in 2.8% of donors vs 1.5% of nondonors. Donors using oral contraceptives had higher S-ferritin, median 33 micrograms/l compared with nonusers, 22 micrograms/l, and a lower frequency of depleted iron stores, 29% vs 39%. Ideally, the frequency of phlebotomy should be adjusted according to S-ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with predonation values greater than or equal to 124-125 g/l should be allowed to undergo phlebotomy.
A longitudinal study of iron status markers (haemoglobin (Hb), serum (S-) iron, S-transferrin, transferrin saturation, S-ferritin) was performed in 31 chemotherapy treated patients with small cell lung cancer. At discovery, eight patients were anaemic (Hb less than 121 g l-1). Hb, S-iron and transferrin saturation were lower (P less than 0.01), and S-ferritin higher (P less than 0.01) than in healthy subjects. Chemotherapy induced an immediate fall in Hb (P less than 0.003), increase in S-iron (P less than 0.003) and transferrin saturation (P less than 0.001). Later in the disease a fall in S-transferrin (P less than 0.006) and an increase in S-ferritin (P less than 0.02) occurred. Thirty patients died during the 2 years observation. S-ferritin at discovery was correlated to performance status score (r = 0.57, P = 0.01) and to survival (r = -0.63, P less than 0.0002). Patients with S-ferritin less than or equal to 400 micrograms l-1 (n = 13) had longer survival than those with S-ferritin greater than 400 micrograms l-1 (n = 18) (P = 0.004).