Lung fibrosis induced by Thorotrast.

A 63 year old woman developed progressive shortness of breath, pulmonary hypertension, and respiratory failure and died from pulmonary fibrosis 45 years after thoracic fistulography with Thorotrast. Bouts of acute respiratory failure occurred with features of noncardiogenic pulmonary oedema. Lung tissue obtained by biopsy and at necropsy showed abundant radioactive particles of thorium dioxide in the lungs. The particles were congregated in the walls of blood vessels and in perivascular fibrous zones, consistent with a causal role of Thorotrast in the development of lung fibrosis. It is suggested that the fibrosis was due to the combined effects of alpha radiation on the interstitial perivascular zones and of recurrent pulmonary oedema due to endothelial damage.

Perinatal renal vein thrombosis. Sonographic demonstration.

The use of ultrasound (US) in the diagnosis of renal vein thrombosis (RVT) remains ill defined because the classical features lack specificity. The authors report three cases of renal vein thrombosis with a common US pattern: hyperechoic streaks in the interlobulary spaces confirming previous reports with the same pattern. The pattern has been observed in neonates as well as in utero. Associated vena cava thrombosis was present in two cases. This sign might be a specific sign of RVT.

Cell population kinetics in dog and human adult thyroid.

Cell population kinetics was studied by bromodeoxyuridine (BrdU) histochemical and 3H thymidine radioautographic labelling in dog thyroids. In-vivo labelling with BrdU and in-vitro labelling of incubated slices with 3H thymidine gave similar results. This validates the use of in-vitro labelling of slices for the study of cell kinetics in the thyroid. In-vitro labelling of human thyroid slices demonstrated a labelling index of 13.4 x 10(-5) for follicular cells; assuming an S phase of 10 h, this corresponds to a turnover time of the order of 8.5 years for the follicular cells. Stromal cells appear to turn over faster. These results show for the first time that human thyroid cells divide about five times during adulthood and therefore that the steady state level of thyroid cell mass results from a balance between cell division and cell loss. A shorter turnover time was found as expected in the thyroid of an adolescent and in follicular colloid nodules.

Wegener's granulomatosis presenting as acute respiratory failure with anti-neutrophil-cytoplasm antibodies.

Anti-neutrophil-cytoplasm antibodies recently have been reported as serologic markers of Wegener's granulomatosis. We describe two cases in which this test appeared to be of great value in the diagnosis of Wegener's granulomatosis presenting as acute respiratory failure, a clinical setting in which it may be the only diagnostic test that can be safely and easily performed.

Inhibition by monensin of dog thyroid secretion in vitro.

Monensin, a carboxylic ionophore, raises the pH of prelysosomal and lysosomal compartments and inhibits lysosomal protein degradation. We tested this drug in dog thyroid slices to ascertain the role of lysosomal pH in thyroglobulin hydrolysis and hormone secretion. Monensin (10(-7)-10(-5) M) and another carboxylic ionophore, nigericin (10(-7)-10(-5) M), inhibited in a concentration-dependent manner TSH-stimulated secretion of T4, T3, and iodide. This inhibition was not toxic since: 1) 10(-5) M monensin did not affect TSH stimulation of protein iodination and cAMP accumulation; and 2) the inhibition was reversible. Secretion was blocked at a postphagocytotic, presumably lysosomal step because the time lag for the fall in secretion rate after 10(-5) M monensin addition was 19 min +/- (SD) 3 min (six experiments), i.e. the same as after lysosomotropic amine addition and significantly shorter than after addition of cytochalasin B (time lag, 43 min +/- 7 min, nine experiments), an inhibitor of phagocytosis. In addition, 10(-5) M monensin blocked the TSH-induced formation of apical pseudopods and colloid droplets and induced a swelling of the Golgi structures. In conclusion, monensin interfered with phagocytosis and with a postphagocytotic, presumably lysosomal, step in secretion by dog thyroid in vitro. Our data provide the first biochemical evidence, in the intact cell, that an acidic pH in the prelysosomal and/or lysosomal compartment is necessary for thyroid hormone secretion.

Skeletal involvement in sarcoidosis: a case report.

A patient is described in whom sarcoidosis caused a pathological fracture of the middle phalanx of the little finger. A bone scan showed increased uptake. She was treated by resection of the diseased area and bone grafting, which led to bone healing. The bony manifestations of sarcoidosis are reviewed.

Human heart-lung transplantation: physiologic aspects of the denervated lung and post-transplant obliterative bronchiolitis.

Eighteen sequential follow-up measurements of pulmonary function were obtained over a period of 21 months after heart-lung transplantation in a patient who had undergone surgery for end-stage pulmonary lymphangioleiomyomatosis. In the early postoperative period, there was a moderate decrease in VC and TLC but gas exchange was maintained at essentially normal levels. The most conspicuous features of postoperative lung function were a very low airway resistance and an increase in FEV1/VC ratio above 95%. These alterations were associated with an unusual shape of the maximal expiratory flow-volume (MEFV) curve. Instead of showing a uniform decrease in expiratory flow as expiration proceeds to residual volume, the post-transplant MEFV curve showed a peak followed by a gently sloping plateau ending at a knee where flow suddenly fell. The knee occurred after exhalation of 80% VC. From the sixth postoperative month, the patient developed rapidly increasing air-flow obstruction, which proved to be due to obliterative bronchiolitis. As air-flow obstruction worsened, the knee on the MEFV curve progressively occurred at a higher lung volume, the flow plateau shortened, and flow after the knee became smaller at a given volume. From the ninth postoperative month, it was no longer possible to identify a plateau-knee configuration on the MEFV curve, which resembled that seen in severe obstructive airway disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental technician's pneumoconiosis. A report of two cases.

Diagnosis of pneumoconiosis was made in 2 dental technicians presenting with interstitial lung disease. The occupational origin of inhaled dust was confirmed by mineralogic analyses, which disclosed mainly large amounts of chromium-cobalt-molybdenum particles originating from Vitallium prostheses, but also showed abrasives (silica and silicon carbide) and asbestos in 1 patient. The presence of Vitallium and its chemical stability in bronchoalveolar lavage and lung several years after cessation of exposure confirm the resistance of this alloy to corrosion by body fluids. This contrasts with the high solubility of cobalt described in cobalt or hard metal disease. We suggest that dental technician's pneumoconiosis is a complex pneumoconiosis distinct from silicosis, asbestosis, or hard metal disease and that Cr-Co-Mo alloys play a role in its pathogenesis.

[Percentage of epithelial cells, fibroblasts and endothelial cells in the dog thyroid]. / Etude du pourcentage de cellules épithéliales, fibroblastes et cellules endothéliales dans les thyroïdes de Chien.

The proportions of various cells types were studied in the thyroids of a variety of dogs used for laboratory experiments. A remarkable constancy was found with epithelial cells accounting for 70% of the total number of cells. The relative proportions of luminal and epithelial cells spaces were also very similar in different animals (47% and 26% respectively).

[Thymoma and pregnancy. Apropos of a case]. / Thymome et grossesse. A propos d'un cas.

A case of thymoma associated with pregnancy is reported. This association is extremely rare (8 described cases) and the clinical outcome is most frequently unfavorable for the mother. The diagnosis was given by a standard chest X-ray performed routinely post-partum. Sixteen months after total surgical extirpation of the tumor and adjunctive radiotherapy the patient is still in complete remission. The presented case is discussed with reference to a review of literature.

Neonatal hepatitis with obstructive jaundice in an SZ heterozygous alpha 1-antitrypsin-deficient boy and destructive lung disease in his SZ mother. A review of the literature.

SZ-Alpha 1-antitrypsin deficiency, leading to severe transient neonatal cholestasis with mild hepatitis is rare. In our patient, intrahepatic bile duct hypoplasia was suspected. Since cholecystography and hepatic scintigraphy failed to reveal intrahepatic bile ducts, a diagnostic surgical liver biopsy was performed. Typical intrahepatocytic PAS-positive granules and a low serum alpha 1-antitrypsin concentration allowed a correct diagnosis of the SZ phenotype. The administration of an elementary diet quickly improved the clinical condition of our patient. Follow-up studies of this case and others will allow a better establishment of prognostic criteria and help in genetic counselling.

Massive vitamin A intoxication with ascites and pleural effusion.

Vitamin A intoxication was diagnosed in a 14-year-old girl who presented with massive exudative ascites and right pleural effusion, impaired liver enzymes, and hypertriglyceridemia. Electron microscopy of liver biopsy material demonstrated numerous perisinusoidal lipid-filled Ito cells. The patient had taken 100-200,000 I.U. vitamin A per day for 15 months. Serum vitamin A level remained elevated for 4 months after vitamin discontinuation. The unusual severity of portal hypertension was documented by a high wedged hepatic vein pressure level. The ascites occurred 2 months after vitamin A had been discontinued, probably owing to particularly slow mobilization of large hepatic stores of vitamin A. Portal hypertension disappeared after a 6-month low vitamin A diet, but the liver biopsy failed to demonstrate any decrease in number or size of Ito cells, suggesting that lipid venous obstruction is unlikely to be the only mechanism responsible for portal hypertension in vitamin A-induced liver disease.

Prostacyclin production by the deendothelialized rabbit aorta.

The acute effect of in vitro deendothelialization on the production of prostacyclin (PGI2) by the rabbit aorta has been investigated. The effectiveness of removing endothelium by rubbing it against filter paper or scraping it with a scalpel was demonstrated by scanning electron microscopy and en face examination after silver staining. Endothelium removal produced an immediate stimulation of PGI2 release, resulting in 408% of the control after rubbing and 367% of the control after scraping, during the first 30-min period of incubation. This increased production of PGI2 gradually declined over time to reach values similar to the control after 2h. At that time, the deendothelialized aorta was totally unresponsive to the stimuli that increase PGI2 release in the intact aorta (acetylcholine, ADP, ionophore A23187, and arachidonic acid). The enhanced production of PGI2 in the deendothelialized aorta was associated with an increased release of free arachidonic acid (353% of the control): in contrast with PGI2, this stimulation was maintained for at least 150 min. A transient exposure of the deendothelialized aorta to ibuprofen (250 microM) was followed by a rebound of PGI2 production, which was also prolonged by BW-755C (3-10 microM). In conclusion, removal of the endothelium triggered an immediate and sustained mobilization of free arachidonic acid in the rabbit aorta: the resulting increase of PGI2 production was short-lived, probably as a consequence of cyclooxygenase self-inactivation. Our results indicate that the subendothelium has a significant capacity to produce PGI2, but that this capacity is expressed only briefly.

Inhibition by lysosomotropic amines of dog thyroid secretion in vitro.

The lysosomotropic amines are well-known inhibitors of lysosomal protein degradation. These drugs were used in dog thyroid slices to ascertain the role of the lysosome in thyroglobulin hydrolysis and in hormone secretion. NH4Cl (1-20 mM) and chloroquine (5-500 microM) inhibited, in a concentration-dependent manner, the TSH-stimulated secretion. The high concentrations of these compounds also inhibited the basal secretion. The inhibition was not toxic since 1) the nonbutanol extractable iodine, an index of follicle disruption, was not increased, except slightly by 20 mM NH4Cl; 2) the compounds did not inhibit the TSH-induced stimulation of protein iodination; 3) the inhibition of secretion caused by these compounds was reversible; 4) the ultrastructural changes induced by NH4Cl were reversed after its withdrawal. The inhibition of secretion was presumably related to the lysosomal trapping of the drugs because: 1) the time lag for the fall in secretion rate after drug addition was shorter than for the inhibition of secretion at the level of pseudopod formation by carbamylcholine and cytochalasin B; 2) for NH4Cl this delay and the degree of inhibition were modulated by the [H+] gradient between the medium and the lysosome; 3) 20 min after NH4Cl addition, 92% of the lysosomes were vacuolated and swollen (median section area, 126 mu2 vs. 50 mu2 for the controls) and 8% of the lysosomes were swollen and still dense (median, 206 mu2); 20 min after chloroquine addition, 90% of the lysosomes remained dense and had a significantly higher section area (median, 79 mu2) than the controls (P less than 0.001), whereas 10% of the lysosomes were vacuolated and large (median area, 438 mu2). The number of pseudopods measured by scanning electron microscopy significantly decreased only after 1 h (P less than 0.001). This late decrease could not account for the early block of secretion and suggested a lack of membrane recycling. In conclusion, lysosomotropic amines interfere with a post phagocytotic, presumably lysosomal, step in secretion by dog thyroid. These data constitute the first biochemical evidence in the intact cell of the role of lysosomes in TSH-induced thyroglobulin hydrolysis and thyroid hormone secretion.

[The diagnostic value of asbestos bodies in mesotheliomas]. / Intérêt diagnostique des corps asbestosiques dans le mésothéliome.

The exposure of asbestos was studied in 31 cases of mesothelioma from case histories and by microscopic mineralogical analysis of the broncho-alveolar lavage fluid (BAL) (31 cases) and of pulmonary tissue (5 cases). When definite exposure had occurred the lavage contained asbestos bodies in every case, except one patient with severe airflow obstruction. The most positive lavages, probably reflecting exposure to industrial amphiboles, were found in patients presenting with radiological evidence of asbestosis. Two patients had positive lavages 50 years after exposure had ceased. The lavage confirmed exposure in 6 out of 11 suspected cases and revealed contamination by asbestos in a further 4 cases, in a group of 6 not known to have been exposed. In 19.3% of cases there was a low concentration of asbestos bodies (less than 1AB/ml of BAL), comparable to what is found in 16.2% of controls from an urban population. An analysis of lung tissue confirmed massive exposure (greater than 20 000 AB/g) in two cases and in particular revealed a significant dust load (greater than 250 AB/g) in patients presenting with a weak positive BAL. Thus it seems that all the positive results should be taken into account. Of the 31 cases, 8 had a BAL without asbestos bodies. These were either mesotheliomas not linked to the inhalation of asbestos, or were the result of false negatives on account of artefacts related either to the BAL technique itself or linked to the technique of mineral analysis. Indeed the microscopic counts of asbestos bodies probably underestimate certain exposures, notably environmental exposure to chrysotile.

Mechanism of cholinergic inhibition of dog thyroid secretion in vitro.

It has been previously shown that carbamylcholine (10(-5) M) decreases TSH-induced cAMP accumulation and hormone secretion in dog thyroid slices. The mechanism of the latter effect has been investigated in this work. The role of a decrease of cAMP level as the sole mediator of the inhibition of secretion was excluded: the inhibition persisted in the presence of 1-methyl-3-isobutylxanthine at 10(-4) M, which completely abolished the carbamylcholine-induced decrease in cAMP. Moreover, carbamylcholine also inhibited secretion when the slices were incubated with 0.4 mM (Bu)2cAMP. Scanning electron microscopic studies showed that carbamylcholine added at the same time as TSH blocked the formation of pseudopods in response to TSH within 2 min. The kinetic and morphological effects of carbamylcholine added at the same time as, or 90 min after, TSH were similar to those of cytochalasin B (3 micrograms/ml). After carbamylcholine addition at time 90 min, the stimulated secretion rate persisted unchanged for 46 +/- 10 min (mean +/- SD) (n = 6). During this period the colloid droplets disappeared from the cells. Carbamylcholine, like cytochalasin B, did not affect the basal secretion, which is independent of phagocytosis. It is concluded that carbamylcholine (10(-5) M) inhibits stimulated thyroid secretion at a step beyond cAMP accumulation by blocking pseudopod formation and not by inhibiting thyroglobulin hydrolysis or hormone diffusion.