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Risk of lung cancer among iron ore miners: a proportional mortality study of 1,075 deceased miners in Lorraine, France.

A proportional mortality study of 1,075 iron ore miners in Lorraine, France, who died between 1960 and 1976 showed a significant excess of lung cancer mortality (proportionate mortality ratio = 2.25). Moreover, proportionate lung cancer mortality increased with the duration of work underground (proportionate mortality ratio = 4.24 for subjects who worked underground for more than 30 years) and was higher among pneumoconiotic (siderotic) miners (proportionate mortality ratio = 3.85) than among nonpneumoconiotic miners. These results were confirmed by a case-control study nested in the mortality study. Smoking habits could not be estimated retrospectively with sufficient accuracy to be taken into account. Although the proportion of smokers among contemporary iron ore miners is larger than in the French male population, occupational factors may also play a role; radiation exposure can be ruled out because there is no detectable radioactivity in the Lorraine mines, but dust exposure may be considered as an etiologic factor owing to the relationship between siderosis and lung cancer.

Adult↗

[Morphologic consideration of heart failure (author's transl)].

The left ventricle in left heart failure can be elliptical, spherical or funnel shaped. There is no firm correlation between the different shapes and the hemodynamics. Left ventricular failure results in dilatation, deformation and loss of funnel function of the left atrium. In more advanced stages of left ventricular failure the pulmonary veins become coiled, dilated and narrow stepwise instead of the normal harmonic narrowing to the periphery. The pulmonary parenchyma exhibits fibrosis and septal siderosis at that stage. Heart failure cells can be observed frequently. In later stages, when pulmonary arteries and the right ventricle is involved, secondary global heart failure develops. Right ventricular failure may lead to necrosis of liver cells with jaundice and elevated levels of liver specific enzyms. Primary global failure has no hemodynamic consequences on the pulmonary circulation, as long as left and right ventricular failure are of equal severity. If one form prevails, the clinical picture will be that of left or right ventricular failure respectively.

Adolescent↗

[Hepatic pathology in beta-thalassemia major].

Liver function has been evaluated in 74 patients (aged 9 months to 19 years) with beta-thalassemia major. They were selected from 212 patients because their transaminase levels were three times higher than normal for over three months. In 36 of these subjects BSF clearance test was performed. In the majority of patients (70%) average GPT serum values were increased (66.33 +/- 35.41 U/L) while only a few of the youngest age group exhibited normal values. The transaminase level showed a direct relationship with age, ferritin level and transfusional iron. Furthermore a direct correlation was found between iron and gamma globulin levels both being related to age. Test for viral hepatitis markers showed that 60% of all the subjects studied had had HBV infection. Twenty-six of the 36 patients who underwent BSF test had normal values in the first part of the clearance curve, 8 others showed moderate changes while only the 2 remaining revealed severe alterations. The second part of the curve was abnormal in 34 and markedly altered in 2 subjects. Mean GPT serum values correlated with the first part of BSF clearance curve and BSF 45' values correlated with transfused iron. Siderosis, fibrosis, chronic inflammatory infiltration and vacuolar degeneration were seen at liver biopsy. Histological findings of chronic aggressive hepatitis were shown in two patients with high transaminase and gammaglobulin levels who had markedly abnormal BSF curve.

Adolescent↗

Stainable iron in gastric and duodenal mucosa of primary hemochromatosis patients and alcoholics.

The presence of iron in gastric and duodenal mucosa was investigated with Perl's stain in endoscopic biopsies from 13 patients with overt primary hemochromatosis, 10 chronic heavy alcohol abusers, and 10 patients with nonulcer dyspepsia. In the primary hemochromatosis patients marked iron deposition was found in cells at the base of glands in the gastric body and antrum in nine cases, and in crypt cells and Brunner gland cells of the duodenum in six. Iron was detected in the lamina propria of the stomach in five and duodenum in four cases. A similar distribution of iron overload, usually of lesser degree, was also observed in five alcoholics. Serum ferritin levels and the degree of gastric and/or duodenal iron deposits did not correlate in either hemochromatosis patients or alcoholics. No gastric or duodenal siderosis was observed in nonulcer dyspepsia cases. The absence of gastric and duodenal stainable iron in some hemochromatosis patients and its presence in some alcoholics suggests that the diagnostic value of upper gastrointestinal biopsy in primary hemochromatosis is limited.

Adult↗

[Granulomatous histiocytotic proliferation in the spleen of a two-year old girl (author's transl)].

After remittent fever for several weeks a two-year old girl developed a severe hypochromic microcytic anaemia, rapidly increasing splenomegaly and extensive leftsided pleural effusions. After splenectomy the girl recovered very fast. Elevation of erythrocyte sedimentation rate, sideropenia and microcytosis needed several months for normalisation. Histopathological examination of the enlarged spleen (weight 530 g) and regional lymph nodes revealed a marked granulomatous histiocytotic proliferation with erythrophagocytosis and siderosis. Considering morphological and clinical aspects the association of the reported case with histocytosis X seems to be justified.

Anemia, Hypochromic↗

[Induction, characterization and isolation of preneoplastic hepatocytes following combined treatment with 2-acetaminofluorene and ferric nitrilotriacetate].

Daily administration of ferric nitrilotriacetate (5 ml/Kg b.w./day i.p.) induces in a few weeks liver siderosis; continuous treatment of the same animals with the carcinogen 2-Acetaminofluorene (300 mg/Kg of diet) results in the appearance of several iron devoid hyperplastic areas or nodules, where enzyme histochemistry reveals gamma-GT activity as well as G-6-Pase disappearance. The perfusion of the liver with calcium-free Hanks solution plus collagenase allows an easy isolation of the hepatocytes, whereas a partial separation of the different kinds of cells can be achieved by isopycnic gradient sedimentation.

2-Acetylaminofluorene↗

Congenital dyserytropoietic anaemia, type II (HEMPAS) in three siblings.

These siblings of a Czech family aged 21, 19 and 6 years, respectively, with congenital dyserythropoietic anemia, type II, (HEMPAS) are reported. In two elder siblings ferrokinetic studies revealed a rapid plasma 59Fe clearance, markedly decreased erythrocyte incorporation and shortened 51Cr red-cell survival. Direct anti-globulin test was found positive in one of them. Further investigations revealed low values of blood plasma cholesterol, total lipids, beta-lipoproteins, beta-carotine and vitamin E and A as well as low values of the prothrombin complex. Liver biopsy demonstrated siderosis and disseminated intravascular coagulation in the liver in both patients. The possible reasons for these humoral aberrations are discussed.

Adolescent↗

[Long term effects of low concentrations of noxious gases on the respiratory system: results of an epidemiological study among iron mines workers in Lorraine (France). (author's transl)].

An epidemiological study of 1,178 iron-mine workers in the Lorraine basin was conducted in order to assess the long-term effects on the respiratory system of low concentrations of noxious gases produced by the machinery and explosives in use. The subjects were selected at random from 5,300 workers who were aged between 35 and 55, had been in the mines for at least five years and who were free from radiological abnormalities such as siderosis, tuberculosis, fractured ribs, etc. For each subject a standard questionnaire (E.C.S.C. bronchitis/emphysema questionnaire) was completed and a clinical examination was performed along with the following tests-vital capacity; forced expiratory volume in 1 second; residual volume; acetylcholine test; steady state CO test for calculation of total and partial transfer functions. A venous blood sample for the determination of blood CO was taken as the subject left his place of work.

Adult↗

[Iron in bone marrow].

In the bone-marrow, non-haemoglobin iron can predominantly be found in the reticulum. Slight granules containing iron can also be observed in parts of erythroblasts by means of the Berlin blue reaction. These cells are called sideroblasts. In chemical respect, non-haemoglobin iron consists of ferritin soluble in water and haemosiderin insoluble in water. Erythroblasts will only take their iron from plasma transferrin. For the most part, this iron uptake is being regulated by erythropoietin adapting erythropoiesis to the oxygen requirements of the tissue. The iron contained in erythroblasts is predominantly utilized for haemoglobin synthesis in these cells. A slight part is being taken up by ferritin. The bone-marrow reticulum will phagocytise aged erythrocytes and store liberated iron as ferritin and haemosiderin. Part of the iron is being delivered again to plasma transferrin. With constant serum iron level the liberation of iron from the reticulo-endothelial tissue must correspond to the iron uptake by erythropoiesis. The absence of iron capable of being coloured in the bone-marrow reticulum is considered to be a reliable parameter of iron deficiency. It enables the diagnosis of iron deficiency anaemia to be made even in those patients with serum iron level and a total iron binding capacity lying within the normal range and no hypochromia of erythrocytes being present. It enables iron deficiency anaemia to be separated from sideropenic anaemia with reticulo-endothelial siderosis in differential-diagnostic manner. Even in patients with sideroblastic anaemia, iron colouring of bone-marrow smears is required for ensuring the diagnosis. Recently, a separation has also been made for idiopathic anaemia with abnormal sideroblasts. In these patients there is an increased risk for acute leukemia to develop.

Anemia, Hypochromic↗

[The urinary elimination of cobalt 57 in iron-deficiency anemia and in iron-overload states].

The authors used the 57 Co urinary excretion test to assess the intestinal absorption of iron in anemia associated with hypoferrinemia and in iron overload states. Among the anemia associated with hypoferrinemia, a high elimination of 57 Co had been found in all patients (15) with post-haemorrhagic iron deficiency anemia. Conversely, this elimination was very low in all 10 patients with anemia due to chronic inflammatory diseases. Moreover the test detected few iron deficiency anemia due to a decreased intestinal absorption of iron. In the iron overload states, the test had been performed in 2 subgroups of patients : chronic anemic patients with transfusional iron overload and hemochromatosis without anemia. In the transfusional iron overload group, 19 patients with thalassemia major who are routinely transfused have a moderate decrease of the 57 Co excretion. This finding probably reflects a continuing intestinal absorption of iron. On the other hand, 6 patients with acquired idiopathic sideroblastic anemia have a very low excretion. In the non anemic hemochromatosis, a high urinary level of 57 Co was present in 5 patients with idiopathic hemochromatosis when it was lower and variable in 6 patients with alcoholic siderosis. Using Wilcoxon, Mann and Whitney's non parametric test, there is a significant difference between the results of both groups. So, in idiopathic hemochromatosis, the high urinary level of 57 Co reflects an inappropriately high absorption of iron in spite of the iron overload and the test may be of value in detecting asymptomatic carriers of the disease.

Adolescent↗

[Hemorrhagic portal hypertension with soft liver].

Over 14 years the authors have observed 6 adults with a special form of portal hypertension revealed by massive gastrointestinal hemorrhages due to rupture of voluminous esophageal varices. Though first suggested by huge enlargement of the spleen (5 out of 6 cases), cirrhosis was eventually discounted by laparoscopy and laparotomy. The liver was of normal volume, smooth (never nodular) and above all soft to the touch, to the biopsy needle and to the surgeon's hand. The histologic lesions of the liver were minimal and heterogeneous: fibrosis without cirrhosis (2 cases), isolated and mild steatosis (2 cases), one non-specific lymphohistiocytic granuloma (2 cases), moderate myeloid metaplasia (2 cases), hepatic siderosis without fibrosis (1 case), sinusoidal congestion (3 cases). Normality of the portal vein was evidenced by angiography (5 cases) or inferred from the elevated porta-caval gradient (1 case), and was confirmed once on autopsy. Sus-hepatic catheterization was performed in every case and provided the following information: right atrial pressure always normal, sus-hepatic veins normal, porta-caval gradient normal or slightly elevated in 4 patients (suggesting presinusoidal block) and obviously elevated in the other two (as in post-sinusoidal block). The minimal histologic lesions of the liver, the normality of the portal vein, the lack of sus-hepatic obstruction, and the variable porta-caval gradient make it impossible to localize the obstacle (if any) and thus say what is the mechanism of portal hypertension with soft liver. In the absence of elevated splenic inflow, this hypertension has to be classified as essential or idiopathic. Soft consistency of the liver has never been reported before in such cases.

Aged↗

Chronic liver disease in haemodialysis patients.

Elevated serum alanine aminotransferase (ALT) for more than one year was found in 36 (28.8%) of 125 patients on maintenance haemodialysis. In 10 the ALT returned to normal spontaneously but in 26 it remained high. Liver tissue from 21 patients with high ALT and seven with normal ALT was examined. Statistically significant correlations were found between the mean ALT during the year prior to the biopsy and assessments of the lymphocytic infiltration (p less than 0.001), fibrosis (p less than 0.001) and amount of silicone particles in the liver (p less than 0.001). Epithelioid cell granulomata, lobular and portal macrophages and perivenular fibrosis were related to silicone particles. Lymphocytes were not spacially related to the particles; nevertheless, there was a significant correlation between amounts of silicone and lymphocytic infiltration (p less than 0.01). No associations were found between high ALT, hepatitis B serology, serum ferritin, parenchymal siderosis, propensity to fluid overload, alcohol abuse and HLA-B8.

Adult↗

Chloroquine in treatment of porphyria cutanea tarda. Long-term efficacy of combined phlebotomy and high-dose chloroquine therapy.

The combined treatment with phlebotomy and high-dose chloroquine for PCT is described and 21 patients treated were followed up for periods of up to 6 years. Clinical and laboratory remissions were experienced by all patients. The urinary excretion of porphyrin and serum hepatic enzyme levels rose rapidly during therapy and then fell, mostly to levels well below that before treatment. The periods required for normalization of laboratory tests, median value, were 1.5 months for liver enzymes and 7 months for uroporphyrins. Clinical symptoms soon disappeared, blistering within 3 weeks and skin fragility within 12. Mild nausea or subfebrility was noted in some cases, but no other serious acute or chronic adverse reactions were observed. Clinical or biochemical relapse appeared in 9/21 (43%) patients who were then retreated. Relapsing cases showed a symptomfree period of 1-2.5 years after each treatment. Liver biopsy was performed in 4 relapsing cases prior to the repeated treatment and showed only mild siderosis and a mild fatty infiltration consistent with pathological liver findings in PCT but no evidence of chloroquine-induced permanent liver damage. The longest symptomfree period observed up to date was assessed for 7 patients who were followed up for more than 2 years after 1 single treatment. Four (57%) of them were symptomfree 5-6 years and no clinical or biochemical signs of relapse were observed. Our data confirm the efficacy of the high-dose therapeutic procedure, and the combined regimen with 1-2 phlebotomies prior to the chloroquine administration seems to be a safe procedure without any serious side effects. Our findings are discussed in relation to other current therapeutic modalities.

Adult↗

Hepatic iron clearance from serum in treated hemochromatosis.

Hepatic iron uptake from transferrin has been studied in 7 patients with treated hemochromatosis. When compared with a control group with similar serum iron and transferrin saturation the hemochromatotics had a significantly higher 4-hr iron uptake value. Uptake in the precirrhotic and cirrhotic hemochromatotics was not significantly different, suggesting the existence of a cellular abnormality of hepatic iron metabolism in this disease. The results provide an explanation for the development of siderosis in some patients with idiopathic hemochromatosis and a normal serum iron concentration.

Adult↗

Ultrastructural abnormalities in carcinogen-induced hepatocellular altered foci identified by resistance to iron accumulation.

Hepatocellular altered foci were induced in rat liver by cycles of feeding of N-2-fluorenylacetamide and were distinguished by their resistance to iron accumulation following production of hepatic siderosis by dietary administration of 8-hydroxyquinoline and ferrous gluconate. The foci were readily identified by their iron exclusion in plastic-embedded sections stained for iron. Sections from iron-free regions processed for electron microscopy permitted ultrastructural study of cells in foci identified by reduced cytoplasmic ferritin. Altered foci of the eosinophilic type produced by cyclic feeding of carcinogen for 16 weeks were composed of both normal-appearing hepatocytes and others with ultrastructural abnormalities, including increased agranular reticulum with associated glycogen particles, decreased rough endoplasmic reticulum with reduced length of cisternae, degranulated rough vesicles, altered and displaced Golgi complexes, and abnormal bile canaliculi. At 12 and 24 weeks after cessation of carcinogen exposure, cells in persistent eosinophilic foci continued to display ultrastructural abnormalities. They possessed increased rough endoplasmic reticulum with rather regular cisternal arrangement and relatively increased smooth endoplasmic reticulum. Golgi complexes were abnormal. Bile canaliculi were abnormal and occasionally increased in number. Nuclei displayed prominent nucleoli. Cells in a basophilic focus were characterized by the presence of numerous free polyribosomes diffusely scattered throughout the cytoplasm, distended rough endoplasmic reticulum with loss of parallel-stack and hypertrophic dilated Golgi complexes, and prominent marginated nucleoli. The finding that persistent foci continued to display ultrastructural abnormalities, some of which changed or progressed in the absence of further carcinogen exposure, suggests that the persistent iron-excluding foci are a permanently altered population.

2-Acetylaminofluorene↗

[Clinical aspects of the radioimmunological determination of serum ferritin].

Personal experience confirms the diagnostic value of serum ferritin estimation in the iron deficient microcytic anemia, where there are low levels. The clinical significance of the test is restricted by the not negligible incidence of levels like that of iron overload in the hepatic and neoplastic diseases. In hepatic diseases the test resulted to be related to the changes of serum transaminases. In malignant neoplasms the high serum ferritin levels had been only sometimes associated with transfusional siderosis.

Adult↗

Some aspects of iron metabolism during acute viral hepatitis.

In the acute phase of acute viral hepatitis high serum iron and serum ferritin levels were found in all patients. The normalisation of the serum ferritin concentration parallelled that of the serum glutamic pyruvic transaminase activity. However serum iron levels remained elevated for a long period of time. Chemical analysis of liver tissue showed a low total liver depot iron concentration during the first two weeks of the disease, indicating that the high serum iron levels are caused by iron liberation from disintegrated hepatocytes. Patients studied after two weeks showed higher liver iron concentrations, in particular the non-ferritin iron fraction, reflecting iron accumulation in the reticulo-endothelial system. Indeed, histological examination in the patients studied after two weeks showed sinusoidal lining cell siderosis in addition to "diffuse iron" in clusters lining cells which in electron microscopical studies proved to be macrophages. These cells showed a positive immunohistological reaction for ferritin protein. It is suggested that during acute viral hepatitis two mechanisms act together, i.e. changes in iron metabolism caused by damage of the main iron depot organ (specific liver pathology) and changes in iron metabolism common to all infectious processes.

Acute Disease↗

[Early diagnosis by means of flow volume curves in workers with respiratory exposure (author's transl)].

In 432 electric welders and 420 not respiratory exposed workers the information value of spirometry (VC, FEV1) and flow volume curves (PEF, V2/V1, V50, V75) was examined taking into consideration the influence of age, smoking and occupational exposure. Despite the higher frequency of chronic bronchitis and pulmonary siderosis in exposed workers no influence of welding fumes on the above mentioned parameters could be shown. Comparing different smoking groups all parameters (with the exception of VC) exhibited the same trend, the FEV1 at the top regarding significance and weight. These results don't support a wider use of flow volume curves in the screening of not selected groups of different exposure. Whether the compared methods can lead to different qualitative or prognostic informations should be examined further in studies comparing functional and morphological data and in epidemiological follow-up studies.

Adult↗