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PubMed2004

Sirolimus-associated diffuse alveolar hemorrhage.

Sirolimus is an immunosuppressive medication used in transplant recipients. To our knowledge, we describe the third reported case of alveolar hemorrhage in association with sirolimus. Fever, dyspnea, hemoptysis, and lung infiltrates resolved rapidly with cessation of sirolimus therapy both initially and after reinstitution of the drug. Unlike previous reports, our patient had no evidence of lymphocytic alveolitis but rather marked macrophage hemosiderosis, suggesting that sirolimus pulmonary toxicity may manifest through 2 separate mechanisms. Our case highlights an uncommon but potentially lethal manifestation of sirolimus pulmonary toxicity.

Biopsy↗
PubMed2006

A blue kidney--chronic renal failure as a consequence of siderosis in paroxysmal nocturnal hemoglobinuria?

Acute renal failure is a known complication during hemolytic crisis in paroxysmal nocturnal hemoglobinuria (PNH). However, chronic renal failure is rare despite the well-known spectacular hemosiderosis of the kidneys due to chronic hemolysis. Here, we report about a 74-year-old man with PNH who developed acute on chronic renal failure after an episode of intercurrent urinary tract infection and subsequent hemolytic crisis. Mild chronic hemolysis, well-documented over the past decade, had long been considered the cause of a constantly declining glomerular filtration rate. Accordingly, magnetic resonance imaging during admission demonstrated marked siderosis of both kidneys, supporting the hypothesis that chronic renal failure (CRF) was likewise related to PNH. However, a renal biopsy revealed acute tubular necrosis and distinct renal siderosis, as expected. Additionally, tubulointerstitial injury and global glomerular sclerosis, best classified as arterionephrosclerosis, were present. In retrospect, these findings were explained by a 15-year history of hypertension and a 4-year medication with cyclosporine. Careful diagnostic workup including a renal biopsy is mandatory, given a misleadingly suggestive correlation between chronic hemolysis and CRF. Chronic renal failure in PNH is a diagnosis of exclusion, even if radiologic evidence of heavy siderosis draws off the physician's attention.

Aged↗
PubMed1982

Spirorchidiasis in loggerhead sea turtles (Caretta caretta): pathology.

Loggerhead sea turtles (Caretta caretta) from the Atlantic seaboard (Florida to Massachusetts) were examined at the Marine Pathology Laboratory, University of Rhode Island, from March through December, 1980. Three genera of blood flukes (spirorchids) were found in 14 (33%) of the 43 turtles. Gross signs in heavily infected animals included cachexia, anemia and enteritis. Histopathological lesions were similar to those present in homeotherms with schistosomiasis. Granulomatous gastritis, enteritis, hepatitis, pneumonitis, and nephritis were present. Acute and chronic vasculitis accompanied metastasis of eggs. Infected animals had severe hepatic hemosiderosis, indicative of the anemia observed grossly. Evidence is presented that spirorchidiasis is prevelent in sub-adult loggerhead sea turtles, is responsible for extensive lesions and may be responsible for significant debilitation and mortality.

Animals↗
PubMed1996

Hemolytic anemia in wild seaducks caused by marine oil pollution.

Clinico-pathological examinations were conducted on wild white-winged scoters (Melanitta fusca) contaminated with fuel oil (Bunker C oil) from a capsized cargo ship in February 1993 in Japan. The erythrocyte count, hemoglobin concentration and hematocrit value in the oiled seaducks all were decreased and numerous immature erythrocytes were observed in blood smears. In addition, hemosiderosis was observed in the liver, kidney, and lung of some birds. We propose that the sea-ducks suffered from hemolytic anemia induced by ingestion of oil, which occurs when the birds preen their oiled plumage.

Alanine Transaminase↗
PubMed1997

Lead toxicosis in a captive bottlenose dolphin (Tursiops truncatus) consequent to ingestion of air gun pellets.

A captive bottlenose dolphin (Tursiops truncatus) in a dolphinarium in Tel Aviv, Israel, had signs of anorexia, weight loss and a reluctance to train over a 4-week period in June 1995 and died shortly thereafter. On necropsy, it had an enlarged, yellow discolored liver, and about 55 air gun pellets in the second stomach. The pellets were composed of 40% lead. Samples of liver and kidney cortex contained 3.6 and 4.2 micrograms/g lead, respectively. There was hemosiderosis in the liver and kidneys, status spongiosus in the brain, and vacuolization in the optic nerve; acid-fast intranuclear inclusion bodies were seen in the kidneys. We propose that chronic lead toxicosis had been induced after the gradual dissolution of the lead-based pellets in the acid environment of the stomach.

Animals↗
PubMed1997

Congenital defects in northern elephant seals stranded along the central California coast.

Eleven cases of congenital anomalies were identified in 210 (5%) juvenile northern elephant seals (Mirounga angustirostris) found stranded along the central California (USA) coast from 1 January 1988 to 31 December 1995. Seven individuals had mild-to-moderate hydrocephalus involving the lateral ventricles bilaterally, or the lateral and third ventricles. Two animals had severe cardiac anomalies: hypoplasia of the right ventricle with overriding aorta, and ventricular septal defect. Other anomalies included single cases of hydronephrosis, focal pulmonary dysplasia, and congenital epidermal angiomatosis. Common intercurrent disease processes were verminous pneumonia and arteritis, verminous enteritis and coliti, and splenic and hepatic hemosiderosis. The more severe anomalies were considered to be the cause of debilitation and stranding. Milder anomalies were found incidentally during routine gross necropsy and histopathologic examination.

Angiomatosis↗
PubMed2001

Health effects following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards.

Permanent approval of shot composed of tungsten-iron and tungsten-polymer for waterfowl hunting by the U.S. Fish and Wildlife Service was pending the results of the present study that examined the health and reproductive effects of the two shot types on mallards (Anas platyrhynchos) over a 150-day period. We collected data pertaining to the effects of tungsten-iron and tungsten-polymer shot on mortality, body weight, organ weight, tissue pathology, and shot erosion. Thirty-two bird groups (sexes equal) of adult mallards were dosed orally with eight #4 steel shot (control), eight #4 tungsten-iron shot, or eight #4 tungsten-polymer shot on days 0, 30, 60, 90, and 120 of a 150-day trial (26 January 1998 to 25 June 1998). An additional 12 mallards (sexes equal) were dosed orally with eight #4 lead shot (positive control) on day 0 of the study. All lead-dosed ducks died by day 25, whereas no ducks died in the other treatment groups. Significant liver hemosiderosis was present in all control and tungsten-iron-dosed males, in five of eight control and three of eight tungsten-iron-dosed females, and in one tungsten-polymer-dosed male examined. The rate of shot erosion was highest for tungsten-polymer shot (99%), followed by tungsten-iron (72%), and steel (55%) shot. Tungsten-iron or tungsten-polymer shot repeatedly administered to adult mallards did not have deleterious health effects during the 150-day trial based on mortality, body weights, organ weights, and histology of the liver and kidneys.

Alloys↗
PubMed1976

[Preventive surgery in the treatment of severely injured eyes: late results, complications, postoperative care (author's transl)].

Definitive reconstruction of the eye is the main objective of surgery in severe trauma. Therefore the damaged lens and vitreous have to be primarily removed in combined injuries to the anterior and posterior segments. 81 cases, treated according to this, have been followed-up from 6 months to 6.2 years. 43 have a VA of 0.1 or better, 18 at least a useful visual field. Main causes of blindness in 20 eyes are retinal detachment in 10, hemosiderosis in 4, phthisis in 3 eyes. 8 of the eyes lost through retinal detachment had a massive intraocular hemorrhage during the post-traumatic period. This hemorrhage is discussed as a main factor in development of retinal detachment with a poor prognosis. In 9 other cases of severely injured eyes with a massive posttraumatic intraocular hemorrhage the blood was removed from the vitreous cavity by intraocular irrigations with Ringer's solution. In 4 of these cases visual function could be retained.

Adult↗
PubMed1998

Fertility in female patients with thalassemia.

With recent therapeutic advances, thalassemic patients can now reach adulthood and attain reproductive capacity. Endocrine complications due to hemosiderosis and especially hypogonatotropic hypogonadism, which present either with sexual infantilism and primary amenorrhea or with secondary amenorrhea, are common in thalassemic women. The aim of this study was to estimate the frequency of fertility among our female thalassemic patients. Our population included 50 married women with thalassemia major (TM) and 12 with thalassemia intermedia (TI) who are regularly followed in our thalassemic centers. Of the 50 patients with TM, 7 had primary amenorrhea (PA), 9 had secondary amenorrhea (SA), and 34 had normal menstrual function (NM), as did all the patients with TI. Overall we had 62 women who were able to achieve 90 pregnancies and give birth to 87 healthy babies. Most of our patients became pregnant around the age of 25 years. Associated endocrine complications were rare except in the group of patients with PA, as expected. In all patients with PA and SA, the 17 pregnancies were induced (intercourse 10, insemination 3, IVF 4). In the patients with NM and TI, 66 pregnancies were achieved spontaneously and 7 following induction (insemination 3, IVF 4). There were four twin and one triple pregnancies, which all resulted in premature deliveries. Among the seven couples in which both partners had thalassemia major, sperm donation was used in 5 cases, ovum donation in one case, and one pregnancy was achieved spontaneously. These 90 pregnancies resulted in 69 full-term, 12 pre-term, 7 abortions and 2 stillbirths. No severe obstetric complication was observed except for two patients with preeclampsia. One patient with PA who carried the triple pregnancy developed severe cardiac failure, which was successfully treated. Transfusion requirements were increased during pregnancy. Discontinuation of desferrioxamine resulted in elevation of ferritin levels during the second and third trimesters of pregnancy and after delivery. Nine patients who were examined with cardiac echo had a transient increase of ESD and EDD during pregnancy, with return to normal after delivery. Labor was performed by Caesarian section in 26 births (26%) out of the 81 successful pregnancies. These collected data represent the largest number of pregnancies in thalassemic females reported so far and are clearly encouraging for the ultimate improvement of the quality of life in thalassemic patients.

Adult↗
PubMedDate not supplied

Open lung biopsy.

During 16 years (1958-1974) 327 open lung biopsies were carried out in the Tuberculosis and Respiratory Diseases Research Institute, the 2md and 3rd Surgical Clinic of Charles University in Prague. A modification of the original Klassen's surgical technique with axillary or submammary approach was used. The patients (160 males, 167 women) were referred for biopsy because of various forms of diffuse pulmonary lesions without established diagnosis. The age of the patients varied from 6-72 years, 27 of them, aged over 60, were operated on nothwithstanding their compromised cardiopulmonary function. In 252 (79%) the definite diagnosis with characteristic histology was obtained, and in 70 (21%) only pulmonary fibrosis without exact specification was evaluated. The definite histologic findings were as follows: 102 (31%) diffuse interstitial pulmonary fibrosis (Hamman-Rich), 32 (10%) pulmonary lesions in systemic cardiopulmonary or bronchopulmonary diseases (collagenosis, eosinophilic and other granulomas, Wegener, hemosiderosis, etc.), 42 (13%) pulmonary sarcoidosis, 12 (4%) pulmonary tuberculosis, 45 (14%) pneumoconiosis, mostly silicosis, 24 (7%) neoplastic lesions. Post-operative morbidity of minor importance was 13,5%, mortality 0,3%: One 56 years old woman died 5 days following operation of cardiopulmonary insufficiency. This was an incorrect indication for biopsy based on inadequate evaluation of the patient's initial functional status. The open lung biopsy obtained by minimal thoracotomy is a valuable and well tolerated diagnostic method in cases where diagnosis cannot be obtained with certainty on the base of results of usual investigation procedures.

Adolescent↗
PubMed1999

[Study of the gene of hemochromatosis in first degree relatives of patient with porphyria cutanea tarda].

BACKGROUND: Porphyria cutanea tarda (PCT) is characterized by a deficiency of uroprophyrinogen decarboxylase (URO-D). The activity of this enzyme is decreased in the presence of iron-dependent disorders. A relationship between the hepatic hemosiderosis, which is present in most patients with PCT, and the status of the hemochromatosis gene has been observed. Particularly, two mutations of the gene have been described, one of them (Cys282Tyr) is related to the iron overload and might influence on the development of the clinical signs of PCT. PATIENTS AND METHODS: We have measured the transferrin saturation percentage and observed the status of the hemochromatosis gene in a patient diagnosed with PCT and in five of their relatives. RESULTS: The proband and one sister had a marked increase of uroporphyrins and iron overload, and both had the mutation Cys282Tyr, which was also present in the mother. CONCLUSIONS: This is the first study measuring iron overload and hemochromatosis gene mutations in relatives, and not in patients with PCT. We think that the study of this family justifies the systematic investigation of these parameters in all first degree relatives of patients with PCT, to identify subjects at risk, who can benefit from prophylactic measures and early therapy.

Adult↗
PubMed1999

Beta-thalassemia and pulmonary function.

BACKGROUND AND OBJECTIVE: The survival of patients with beta-thalassemia major and intermedia has improved considerably. This has focused attention on the long-term sequelae of the disease itself and its treatment. The effect of hemosiderosis in major organs (heart, liver, etc) are well-recognized, but the pathophysiology of any lung damage is less clearly understood. We studied lung function changes in 32 patients with beta-thalassemia. DESIGN AND METHODS: Respiratory function tests, CO diffusion and arterial blood gas analysis were performed on 19 patients with beta-thalassemia major (9 F, 10 M) and 13 with beta-thalassemia intermedia (6 M, 7 F). All investigations were performed 24 hours before the patients received a blood transfusion or when they were in a stable state hematologic condition. Echocardiography was performed in all patients and the ejection fraction was employed as a measure of cardiac function. RESULTS: No patient had clinical signs of pulmonary dysfunction. Pulmonary function tests, however, showed a reduction of all main parameters (TLC, FVC, FEV1 and RV) in most patients with beta-thalassemia major, indicating a restrictive type of dysfunction. The pulmonary function of patients with beta-thalassemia intermedia seemed to be preserved. Arterial blood gas values were within the normal range, while in some subjects CO diffusion approached the lower limits of normality. There was no evidence that the observed abnormalities in pulmonary function were secondary to congestive heart failure. INTERPRETATION AND CONCLUSIONS: Iron deposition due to repeated blood transfusions may play a central role in determining lung alterations although the majority of patients are well chelated, suggesting that more than one causal mechanisms could be involved.

Adolescent↗
PubMed1999

Nitrobenzene carcinogenicity in animals and human hazard evaluation.

Nitrobenzene (NB) human cancer studies have not been reported, but animals studies have. Three rodent strains inhaling NB produce cancer at eight sites. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, F344/N male rats respond with liver malignant tumors and thyroid and kidney benign tumors, while females respond with endometrial polyps. Male Sprague-Dawley rats (CD strain) respond with liver benign tumors. NB is oxidized to various phenolic metabolites, while also being reduced in the cecum and systemically in the microsomes to nitrosobenzene (NOB), phenylhydroxylamine (PH), related free radicals, and aniline (AN). Based on structural and mechanistic similarities, NB compares with other animal and human carcinogenic nitroarenes and aromatic amines. Reduced NB first forms the nitroanion free radical, which can react with O2 to form superoxide O2*. Repeated NB dosing produces a persistent redox couple NOB<==>PH in red blood cells (RBCs) that generates met-Hb and expends NAD(P)H. NOB forms activated glutathione (GSH) conjugates. These biochemical effects may lead to critical redox imbalances and macromolecular binding. Known NB effects are hemosiderosis, methemoglobinemia, and anemia--and now dispersed cancer in rodents. On the basis of animal, metabolic and structure-activity studies, NB is determined to be a probable human carcinogen by any route of exposure.

Administration, Inhalation↗
PubMed1999

Nitrobenzene potential human cancer risk based on animal studies.

Inhaled nitrobenzene (NB) in animals produces cancer at eight sites in three rodent strains. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, and F344/N male rats respond with liver malignant tumors and thyroid and kidney benign tumors, while females respond with endometrial polyps. Male Sprague-Dawley male rats (CD strain) respond with liver benign tumors. NB is oxidized to various phenolic metabolites, while also being reduced to nitrosobenzene (NOB), phenylhydroxylamine (PH), related free radicals, and aniline (AN) in the cecum by bacteria and in the body by the microsomes. In reduction, NB first forms the nitroanion free radical, which can react with O2 to form O2*-. Repeated NB dosing produces a persistent redox couple NOB<==>PH in red blood cells that generates met-Hb and expends NAD(P)H. NOB forms activated glutathione conjugates. These biochemical effects may lead to critical redox imbalances and macromolecular binding. Known effects are hemosiderosis, methemoglobinemia, and anemia--and now dispersed cancer in rodents. Based on structural and mechanistic similarities, NB compares with other animal and human carcinogenic nitroarenes and aromatic amines. The cancer hazard evaluation of NB is that it is a probable human carcinogen by any route of exposure. The maximum response is in F344/N male rats which is used for dose-response modelling. The model to estimate the upper 95% confidence limit (UCL95%) of NB human carcinogenicity is a no-threshold, linear low-dose, and multistaged animal model (LMS). The UCL95% of cancer slope is estimated to be 0.11(6) mg/kg/day (mkd). At de minimus risk (1:10(6)), the virtually safe dose (VSD) is estimated to be 9.1 ng/kg/day (nkd).

Animals↗
PubMedDate not supplied

[The effect of bromantane on the erythro- and leukocytic profile of the peripheral blood in rats].

The specific effect of bromantan on blood tissue is demonstrated in rats. In chronic injection in a dose of 30 mg/kg bromantan raised the level of hemoglobin and leukocytes. In doses of 150 and 600 mg/kg it increased at first (3 months) and then reduced the level of erythrocytes, hemoglobin, and leukocytes. Reversible poikilocytosis, granulocytosis, and agranulocytosis were encountered. Hyperchromatosis and hypertrophy of the hepatocytes were found in the tissues of the liver and hemosiderosis was discovered in the spleen. It is suggested that the blood tissue is a "target" in the toxic effect of bromantan.

Amantadine↗
PubMed2000

Chelation therapy in patients with thalassemia using the orally active iron chelator deferiprone (L1).

BACKGROUND AND OBJECTIVE: Excessive hemosiderosis is the main reason for the multi-organ failure observed in multitransfused patients. Deferiprone (1,2-dimethyl-3-hydroxy-pyridine-4-one, L1) is an orally active iron chelator mainly excreted via urine. We conducted a study in order to determine the efficacy and safety of L1 in Greek thalassemic patients. DESIGN AND METHODS: A group of 11 thalassaemic patients entered the study; L1, the Cipla formulation for deferiprone, at a daily dose of 75-100 mg/kg bw t.i.d. was used. After giving informed consent all patients were subjected to clinical examination and biological tests. RESULTS: All patients tolerated the L1 well; there were no significant side effects (except for slight gastrointestinal disturbances for the first days). The net urinary iron excretion ranged from 6.96 to 26.1 mg/24h. Serum ferritin declined within 4-6 months in most of the patients. INTERPRETATION AND CONCLUSIONS: The results suggest that L1 is a rather safe drug which decreases iron overload without causing any considerable side-effects in Greek thalassemics.

Administration, Oral↗
PubMedDate not supplied

Fatal acidosis in a neonate with Pearson syndrome.

We report a neonate who presented with hypotonia, hypoglycemia, and severe lactic acidosis. The patient's acidosis did not respond to bicarbonate replacement and dialysis. Postmortem liver samples revealed portal dilatation, fibrosis, canalicular proliferation, cholestasis, and hepatocellular hemosiderosis. Vacuolization of bone marrow precursors suggested a diagnosis of Pearson syndrome. A common mitochondrial DNA deletion of 4,978 bp was found. We emphasize that Pearson syndrome should be considered in neonates with lactic acidosis despite absence of anemia.

Acidosis, Lactic↗
PubMed1975

[Severe light dermatosis following photo therapy in a newborn infant with congenital erythropoietic urophyria].

A newborn infant with hemolytic anemia and hepatosplenomegaly was treated by phototherapy for early jaundice. After 18 h, a dark brown pigmentation of the skin was noticed, leading to the assumption of a bronze baby syndrome. Indeed, the child was suffering from a severe disturbance of liver function. 4 days later, a severe bullous dermatosis with blody imbibition developed, covering all exposed parts of the body surface and reoccurring in many bursts over several weeks despite protection against light. A severe hemolytic anemia was constantly present. The baby died on the 50th day. The diagnosis of erythropoietic porphyria was suggested immediately after the onset of the bullous exanthema and proved by laboratory data as follows: uro- and coproporphyrin in the urine were extremely high, uroporphyrin being mainly of type-I isomer. In red cells, increased amounts of uro-, copro- and protoporphyrins were detected. Massive red fluorescence of erythroblasts (so-called porphyroblasts) in the bone marrow and in the blood could be observed. At autopsy, the liver showed multiple blood-forming areas and severe diffuse hemosiderosis, which is to be explained by a long existing, i.e. fetal hemolysis. Erythropoietic porphyria is such a rare disease that there is no reason to consider it as a general contraindication for phototherapy.

Bone Marrow Diseases↗