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Relationship between oxidative stress, pathology, and behavioral signs of lead poisoning in mallards.

Some of the adverse effects of lead (Pb) may be associated with oxidative damage of lipids, proteins, or DNA. In a previous study a linkage was observed between the susceptibilities of waterfowl species to Pb poisoning with oxidative stress. To investigate this relationship among the individuals of a single species, for 3 wk 4 groups of 12 mallards were fed diets containing high or low levels of vitamin E (20 or 220 UI/kg) and high or low levels of Pb (0 or 2 g/kg). During the first week of Pb exposure, mallards developed hemolytic anemia, and during the second week, signs of neurological impairment. Histological findings in the Pb-exposed mallards were hemosiderosis, demyelinization of sciatic and brachial nerves, and tumefaction of renal tubular epithelium with the presence of intranuclear inclusion bodies. Lipid peroxidation increased with Pb exposure in blood, liver, bile, and brain, but decreased in nerves. Glutathione (GSH) increased with Pb exposure in liver and bile, and its oxidized/reduced ratio only increased in bile. Pb exposure inhibited GSH peroxidase activity (GPX) in plasma, liver, and brain, and decreased protein thiols (PSH) in blood and liver. Vitamin E resulted in significantly lower lipid peroxidation in nerves of control birds relative to unsupplemented controls, but did not alleviate any sign of lead posioning. Pb-induced pathological changes associated with hepatic and nervous functions were significantly correlated with lower GPX activity and PSH concentrations in these tissues rather than lipid peroxidation. Data suggest that inhibition of antioxidant enzymes and interaction with sulfhydryl groups of proteins may play a more important role in Pb poisoning of waterfowl than lipid peroxidation.

Anemia, Hemolytic↗

Oral toxicity of ferric dimethyl-dithiocarbamate (ferbam) and tetramethylthiuram disulfide (thiram) in rodents.

Single oral doses of ferbam, thiram, zineb, or maneb produced central nervous system stimulation followed by depression and alopecia. Ferbam and thiram were more toxic on the basis of weight than zineb; maneb was relatively nontoxic. There was no species difference in acute toxicity between rats and mice. In 13- and 80-wk feeding studies, the toxic effects of ferbam and thiram in rats were similar; however, thiram was more toxic on the basis of weight than ferbam. During the 80-wk feeding study, weight gain was reduced in ferbam-treated rats starting at daily doses of 8 mg/kg in males and 37 mg/kg in females and in thiram-treated rats staring at daily doses of 5 mg/kg in males and 26 mg/kg in females. Food consumption was reduced in proportion to the reduced weight gain. Death occurred in males fed 109 or 331 mg/kg.d ferbam and in males fed 58 or 132 mg/kg.d thiram. Female rats fed 96 mg/kg.d ferbam or 67 mg/kg.d thiram developed alopecia and ataxia, which led to paralysis of the hind limbs. Male rats fed ferbam or thiram had a more severe incidence of squamous metaplasia in the thyroid and fatty infiltration in the pancreas than control males. Ferbam or thiram reduced the incidence of spontaneous nephritis in both males and females. The male rats that were fed 109 or 331 mg/kg.d ferbam and died betweeen 1 and 5 wk had golden pigment in the reticuloendothelial cells of the spleen and in the enlarged mesenteric lymph nodes, associated with hemosiderosis. Moderate tubular degeneration of the testes with atypical spermatids in the epididymis occured in some rats fed 132 mg/kg.d thiram for 13 wk but not in rats fed up to 52 mg/kg.d for 80 wk. Periodic hematologic examination and terminal clinical blood tests did not reveal any severe changes. Ferbam and thiram did not alter the occurrence or latent period of the spontaneous tumors seen in control rats.

Animal Feed↗

Short-term oral toxicity of 2,4,6-trinitrotoluene in mice, rats, and dogs.

The short-term oral toxicity of 2,4,6-trinitrotoluene (alpha-TNT) was determined in dogs, rats, and mice. Single-dose oral LD50s for alpha-TNT in corn oil were 1320 and 794 mg/kg in male and female rats, respectively, and 660 mg/kg in both male and female mice. For multiple-dose studies, dogs were dosed daily for up to 13 wk with alpha-TNT at 0, 0.2, 2.0, or 20 mg/kg by capsule; rats received 0, 0.002, 0.01, 0.05, or 0.25% and mice received 0, 0.001, 0.005, 0.025, or 0.125% alpha-TNT in their diets over the same period. All species receiving the highest doses exhibited anemia, with reduced erythrocytes, hemoglobin, and hematocrit. Alterations were observed in organ weights, including enlarged spleens (accompanied by hemosiderosis) and livers, and depressed body weight and/or body weight gain (temporary in dogs and mice). Alterations in clinical chemistry values included elevated cholesterol and depressed serum glutamicpyruvic transaminase activity in dogs and rats; no effect on serum glutamic-oxaloacetic transaminase activity was observed. Some effects, such as SGPT depression in rats, appeared after 13 wk, suggesting a cumulative toxicity. Reduced testes size was observed in rats at the highest dose regardless of length of exposure. Most of the toxic effects were reversible, but testicular atrophy was not in rats allowed a 4-wk recovery period after treatment. Signs of anemia were present at intermediate dose levels. "No observable effects" levels for alpha-TNT were: dogs, 0.20; rats, 1.42; and mice, 7.76 mg/kg . d.

Anemia↗

Short-term oral toxicity of a 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine mixture in mice, rats, and dogs.

The oral toxicity of a mixture of 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine (1:0.62, w/w) compounds typically found in munitions plant effluents, was evaluated in mammalian species. Single-dose oral LD50s of the mixture were 574 and 594 mg/kg in male and female rats and 947 and 1130 mg/kg in male and female mice, respectively. Long dispersion periods during preparation or ultraviolet irradiation of the mixture lowered the LD50s. In repeated-exposure studies, dogs were given 0.50, 5.0 or 50 mg/kg X d by capsule for up to 90 d. Rats and mice were fed the mixture in the diet at 0.005, 0.05, or 0.5% for 90 d; mice were also fed at 0.25%. Mortality resulted at the highest dose level in each species. All three species showed depression of body weight or body weight gain, depressed food intake, moderate to severe anemia, and alterations in the spleen (hemosiderosis), liver (hepatomegaly), and testes (atrophy) at the highest dose levels. Cholesterol was elevated in rats and dogs after 90 d. Several species differences were also noted. Uric acid values were elevated in rats but not in dogs, serum glutamic-pyruvic transaminase (SGPT) activity was low in dogs but unchanged in rats, and rats developed hypoplasia of the uterus but dogs did not. Signs of anemia were present at the intermediate dose levels. The lowest dose level in all three species was designated at a "no observable effects" level, based on the absence of clearly treatment-related effects. In a 4-wk study, the irradiated mixture fed to rats at 0.003, 0.03, or 0.3% in the diet was less toxic than the unirradiated mixture.

Anemia↗

Subacute toxicity of methylene-bis-(2,6-diisopropylaniline) in the rat and hamster.

Methylene-bis-2,6-diisopropylaniline (MDPA), a chemical having potential application as a polyurethane chain extender or an epoxy curing agent, was administered daily by gavage to male Fischer 344 rats and male Syrian golden FVG hamsters. Rats were administered MDPA at 10.5, 21.0, 42.0, 63.0, or 87.5 mg/kg in corn oil for 5, 10, or 28 d. Hamsters received 87.5 or 875 mg MDPA/kg daily for the same periods. Histopathologic evaluation of rat tissue showed diffuse vacuolar change and periacinar vacuolar degeneration of the livers, with congestion, hemosiderosis, and hematopoiesis in the spleen. Hepatic periacinar vacuolar degeneration decreased in incidence and severity from d 5 to d 28, and livers of rats sacrificed 28 d after cessation of MDPA treatment (d 56) were normal. Hepatic vacuolar change was characterized by lipid inclusions. Electron microscopic evaluation found no structural abnormalities in hepatocytes with a moderate level of lipid vacuolization, while degeneration was seen in cells with extensive vacuolization. Stage III, stage IV, and maximal respiratory rates of mitochondria isolated from livers of test animals were higher than age-matched controls after 28 d treatment. At the high dose (875 mg/kg), MDPA produced liver lesions consisting of periacinar vacuolar change, vacuolar degeneration, hepatocytic swelling, and necrosis in hamsters. The high dose also produced acute toxic tubular nephrosis and a high mortality rate. At a dose (87.5 mg/kg) equuimolar to the high dose in the rat, however, the only lesion observed in the hamster was periacinar vacuolar change. In summary, the degenerative hepatic lesion produced in liver decreased in incidence with continued administration, and higher doses were required to produce this lesion in the hamster than in the rat.

Aniline Compounds↗

Testicular toxicity and infertility in male rats treated with 1,3-dinitrobenzene.

Weanling male Sprague-Dawley rats were gavaged 5 d/wk with 1,3-dinitrobenzene (m-DNB) at dosages of 0, 0.75, 1.5, 3.0, and 6.0 mg/kg X d. Males were bred to untreated females during treatment wk 10 and were killed during treatment wk 12. Although males dosed with 3 mg/kg X d inseminated the females and evidence of mating was observed in males dosed with 6 mg/kg X d, none of the males in these groups sired litters. Diminished sperm production (reduced testicular sperm head counts), decreased cauda epididymal sperm reserves, nonmotile spermatozoa, atypical sperm morphology, decreased weights of the testes and epididymides, seminiferous tubular atrophy, and incomplete spermatogenesis were also observed in these groups. Sperm production was also decreased in males dosed with 1.5 mg/kg X d. Changes in the spleen included increased weight at dosages of 1.5 mg/kg X d or higher and splenic hemosiderosis, which ranged from slight in rats treated with 0.75 mg/kg X d to moderately severe in those dosed with 6 mg/kg X d. The data indicate that m-DNB is a potent testicular toxicant in the male rat, capable of producing extensive damage to reproductive tissues and reproductive failure. Limited data on four rats that received 6 mg/kg X d and were allowed a 5-mo posttreatment recovery period suggested that the testicular effects are at least partially reversible.

Animals↗

Pulmonary lesions in childhood onset systemic lupus erythematosus: analysis of 26 cases, and summary of literature.

The pathological findings in the lungs and related organs of 26 patients (21 female, 5 male) with systemic lupus erythematosus (SLE), with onset of disease before age 20 years, were reviewed. Several categories of lung lesions were found. Chronic interstitial pneumonitis was present in all 26 patients and was severe in 5. Acute pneumonia was present in 20, mild in 13, moderate in 2, and severe in 5. Alveolar hemorrhage, massive enough to cause death in 5, was seen in 18 patients, and pulmonary edema was found in 13. Fourteen patients had hyaline membranes indicative of acute alveolar damage (DAD), 12 had alveolitis obliterans, indicative of prior episodes of DAD, and 9 had bronchiolitis obliterans. Other parenchymal lesions were mild interstitial fibrosis in 12, alveolar hemosiderosis and alveolar overinflation in 10 each, and alveolar septal calcinosis with chronic renal insufficiency in 3. Pleural effusion, pleuritis, or pleural thickening were noted in 15 of 26, 6 of 23, and 7 of 23 evaluable patients, respectively. Vascular lesions were present in 16 as intimal thickening (9), thromboemboli (8), medial hypertrophy (6), calcinosis (3), and vasculitis (2). A previously unreported lesion was chronic (proliferative) peribronchitis, noted in 11 patients. Diaphragmatic lesions included mild variation in fiber size in 7, mild fibrosis in 2, and calcinosis in 1 of 13 evaluable patients. Correlation of the above lesions with previously described lung syndromes in SLE such as lupus pneumonitis, hemorrhagic lung disease, chronic interstitial fibrosis, lupus cor pulmonale, pleurisy, and "shrinking lung syndrome" are discussed.

Adolescent↗

Epidemiology of interstitial lung disease (ILD) in flanders: registration by pneumologists in 1992-1994. Working group on ILD, VRGT. Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding.

Worldwide almost no epidemiologic data are available on the prevalence or incidence of interstitial lung diseases (ILD) in the general population. Therefore, a registration programme of ILD-prevalence was organised by the VRGT (Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding), among about 100 Flemish pneumologists since 1990. Most categories of the classification by Crystal et al. (1) were included and the diagnostic criteria (histology, laboratory tests, clinic, radiology) were registered. The present paper presents the results of 1992-1994: twenty pneumologists had forwarded the summary files of 237 patients to the central office in 1992 (n = 68), 1993 (n = 90) and 1994 (n = 79). The diagnoses that were most frequently made were: sarcoidosis in 27%, idiopathic pulmonary fibrosis in 20%, hypersensitivity pneumonitis in 14% (of which 68% by birds) and collagen-vascular disease in 10% (of which 54% in rheumatoid arthritis). Less frequent causes were eosinophilic pneumonia (4%), inhalation of inorganic material (4%, anthracosilicosis being excluded), histiocytosis X (3%), drugs (3%), angiitis and granulomatosis (2%), pulmonary hemosiderosis (1%), lymphocytic infiltrative lung disease (1%) and lymphangioleiomyomatosis (1%). The order of relative frequencies of the different categories of diseases was the same in the 3 registration years. In 9% of the patients the diagnosis was confined to "undefined fibrosis". The diagnosis was confirmed by histology in 63% of the cases. The overall male-female ratio was nearly one, with, however, a male preponderance in hypersensitivity pneumonitis (22/12), UIP(8/3) and "undefined fibrosis" (14/7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Factors affecting methionine toxicity and its alleviation in the chick.

Young male crossbred chicks were fed crystalline amino acid diets containing excess L-methionine or DL-homocysteine to evaluate factors causing methionine toxicity. Chicks were fed diets containing graded levels of excess methionine from 0% to 2.0%. Rate of gain was reduced at all levels of excess methionine, but the magnitude of depression was greater between 1% and 2% than between 0% and 1% excess methionine. Methionine accumulated in plasma of birds fed excess methionine, but plasma levels of homocysteine, cystathionine and cystine remained essentially unchanged. Spleen iron levels increased linearly and blood hemoglobin decreased linearly when chicks were fed diets containing greater than 1% excess methionine, a level equivalent to about 3 times the chicks' requirement. Chicks fed 1.36% homocysteine had reduced gain and gain:feed values, but spleen iron and hemoglobin levels were unchanged. 3-Methylthiopropionate, a possible metabolite in a proposed alternate pathway, caused a precipitous increase in spleen iron levels. Various methyl sources (betaine, choline, methyl acetate) when fed in excess failed to increase spleen iron levels. Methyl mercaptan and methyl mercaptoacetate likewise did not result in an increase in spleen iron deposition. Both the hemosiderosis condition and the reduced food utilization caused by excess methionine were reversed by supplemental glycine plus threonine.

Animals↗

Efficacy of the D- and L-isomers of N-acetylmethionine for chicks fed diets containing either crystalline amino acids or intact protein.

Chick growth assays were used to evaluate the efficacy and toxicity of the L- and D-isomers of N-acetylmethionine when fed as a source of methionine in crystalline amino acid diets. In agreement with earlier rat studies employing intact protein diets, N-acetyl-L-methionine had a methionine-sparing value of 100% and N-acetyl-D-methionine a value of zero. The former was also observed to be fully effective as a methionine supplement when added to a methionine-deficient diet containing equal protein contributions from soybean, casein and gelatin. Isosulfurous levels of excess L-methionine or N-acetyl-L-methionine were equally growth depressing, but L-methionine elevated spleen iron deposition to a greater extent than N-acetyl-L-methionine. N-acetyl-D-methionine in excess depressed growth only slightly, due entirely to a depression in voluntary food intake, and no evidence of splenic hemosiderosis was observed from this addition.

Amino Acids↗

Adult cockatiels (Nymphicus hollandicus) at maintenance are more sensitive to diets containing excess vitamin A than to vitamin A-deficient diets.

The purpose of this experiment was to examine the physiological responses of adult cockatiels at maintenance to dietary vitamin A (VA) concentrations, and to identify concentrations associated with deficiency and toxicity. Adult cockatiels at maintenance (n = 22, 2-3 y of age) were fed a diet of 0, 600, 3000 or 30,000 microg VA/kg (0, 2000, 10,000 or 100,000 IU), and monitored for signs of VA deficiency or toxicity for up to 706 d. The analyzed diet concentrations were 0, 835, 2815 and 24,549 microg/kg, respectively. After 269 d, birds fed the 30,000 microg/kg VA diet had greater plasma retinal concentrations, markedly intensified vocalization patterns, pancreatitis and multifocal accumulation of lymphocytes in the lamina propria of the duodenum compared to birds fed the 600 microg/kg diet (P < 0.05). The 3000 microg/kg VA diet induced increased plasma retinol, splenic hemosiderosis and altered vocalization patterns (P < 0.05), although not as striking as those induced by the 30,000 microg/kg VA diet. The secondary antibody response was reduced after 225 d and vocalization patterns were altered in birds fed 0 microg/kg VA (P < 0.05), but after almost 2 y there were no changes in body condition, plasma retinol, organ pathology or classical signs of deficiency such as squamous metaplasia of nasal epithelia. Thus, adult cockatiels at maintenance were more susceptible to VA toxicity than to VA deficiency and concentrations > or = 3000 microg VA/kg diet can cause toxicity. It is possible that disturbances in VA nutrition contribute to the widespread incidence of behavioral problems reported in companion birds.

Animals↗

Hepatotoxicity in Wistar rats following chronic methotrexate administration: a model of human reaction.

The effects of ip administration of methotrexate (MTX) on 3-month-old male Wistar rats were studied. We administered log doses from 125 to 2,000 mug/kg, five times per week for as long as 24 months. The massive doses were promptly lethal, and most rats receiving 500 mug or more/kg died within a few weeks. Severe hematopolietic depression and ulcerative gastrointestinal lesions were observed. Truly chronic intoxication was achieved with the lesser doses. Rats in this category developed serious liver damage, namely, varying degrees of fatty metamorphosis, necrosis, atrophy of hepatic cords, and fibrosis. Hematopoietic depletion occurred in the spleen and bone marrow. Hemosiderosis was prominent in the spleen and liver. Pulmonary lesions--chiefly emphysema, occasionally fibrosis--were found less consistently. These studies demonstrated the ability of MTX to induce lesions, most consistently hepatic, in the Wistar rat, and thus have provided an animal model to evaluate protective measures.

Age Factors↗

Subacute inhalation toxicity of aniline in rats: analysis of time-dependence and concentration-dependence of hematotoxic and splenic effects.

In this study, thirty male Wistar rats/group were exposed nose-only to mean analytical concentrations of 9.2, 32.4, 96.5, and 274.9 mg aniline/m3 using an exposure regimen of 6 h/day, 5 days/week for 2 weeks (days 0-11), followed by a 2-week post-exposure period (up to day 28). Serial sacrifices for specialized examinations were performed on days 0, 4, 11, 14, and 28. Clinical signs of toxicity, body weights, hematology, and clinical chemistry tests, including total iron in liver and spleen, splenic lipid peroxidation, organ weights, gross and histological changes in target organs were recorded. No mortality was observed during the study. Rats exposed to 96.5 mg/m3 and above displayed cyanosis, with no apparent progression during the exposure period. The predominant manifestation of toxicity was methemoglobin formation and associated erythrocytotoxicity. The changes observed included anemia, red blood cell morphological alterations (e.g., Heinz bodies), decreased hemoglobin and hematocrit, reticulocytosis, and effects on the spleen (splenomegaly, hemosiderin accumulation, and increased hematopoietic cell proliferation), which gained significance at 96.5 and 274.9 mg/m3. With regard to increased splenic extramedullary hematopoiesis, borderline effects occurred at 32.4 mg/m3. The total content of iron in spleen homogenates increased in a concentration-dependent and time-dependent manner with increasing duration of exposure. The maximum accumulation of iron in the liver and spleen exceeded the respective control levels by approximately 60% and approximately 500%, respectively. Splenic lipid peroxidation and total iron were highly correlated (r2 = 0.93) toward the end of the exposure period. A hepatic hemosiderosis was observed at 274.9 mg/m3. Thus, in regard to erythrocytotoxicity and associated increased splenic sequestration of erythrocytes, iron accumulation and lipid peroxidation 32.4 mg/m3 constitutes the no-observed-adverse-effect concentration (NOAEC). However, spleens of the 32.4 mg/m3 exposure group exhibited a minimal increase in extramedullary hematopoiesis. Exposure to 9.2 mg/m3 was not associated with any significant effect.

Aniline Compounds↗

Pulmonary hemorrhage in deceased infants: baseline data for further study of infant mortality.

Infant lung samples were obtained at autopsy by medical examiner pathologists in five areas of the United States regardless of the cause of death. Lung sections were stained with hematoxylin and eosin. Sixty cases were evaluated for the study. The four sections examined for each case were taken from the anterior and posterior aspects of the right and left upper lung lobes. Histologic sections were scored for the extent of alveolar hemorrhage using the following scoring system: 0, no hemorrhage; 1, focal hemorrhage but less than score 2; 2, patchy, focal hemorrhage not present throughout the section; 3, focal hemorrhage more extensive than score 2 but not meeting the criteria for score 4; 4, patchy focal hemorrhage distributed throughout the section; 5, more extensive hemorrhage than score 4 but not meeting the criteria for score 6; 6, diffuse hemorrhage throughout the section. Total possible scores ranged from 0 to 24. Intraalveolar hemorrhage was observed in 40 cases. Overall, the mean score for the 60 cases was 5 (range, 0-24); for the 40 cases with hemorrhage, 7 (range, 1-24). Scores were compared with other descriptive variables like cause of death; interval between onset of fatal events and death; whether resuscitation was attempted; and pulmonary macrophage counts and hemosiderin scores reported in earlier studies of the same cases. In none of the 60 cases was death attributed to pulmonary hemorrhage or hemosiderosis. Pulmonary hemorrhage tends to be common among deceased infants; more prominent when there is medical treatment or resuscitation during the agonal period; infant position may partially explain distribution of hemorrhage in lungs; postmortem interval may exacerbate pulmonary hemorrhage; and infant deaths caused by acute idiopathic pulmonary hemorrhage (AIPH) or pulmonary hemorrhage/hemosiderosis (PHH) probably are rare. Specific case definitions for AIPH and PHH are needed, along with further study of these conditions.

Autopsy↗

Splenic pathology in thrombotic thrombocytopenic purpura.

To determine splenic pathology in thrombotic thrombocytopenic purpura (TTP), 10 spleens and two accessory spleens were studied. The eight women and two men ranged from 20 to 66 years of age (mean age, 39 years). Three spleens were enlarged. Thrombi were noted in arteries and arterioles in nine specimens: no associated inflammation was seen. Periodic acid-Schiff-positive diastase-resistant hyaline subendothelial deposits (SEDs) were present in all cases. Some arterioles showed a transition between thrombi and SEDs. The presence of platelets or platelet-related material in SEDs and thrombi was documented by factor VIII staining. Hyperplasia of B cells and germinal centers was present in 67%, and periarteriolar concentric fibrosis ("onion-skinning") in 58%. Histiocytes showed prominent iron deposits in 92% and hemophagocytosis in 83% of cases. Extramedullary hematopoiesis was present in 42%. Blood lakes, infarcts, and endothelial hyperplasia were rarely noted; microaneurysms were not seen. Ten spleens from patients with idiopathic thrombocytopenic purpura and 10 age-matched control spleens rarely showed SEDs or hemosiderosis and did not show hemophagocytosis or thrombi. We conclude that subendothelial deposits may be related to platelet thrombi incorporated into vessel walls. Germinal centers and periarteriolar concentric fibrosis may indicate an immunologic role in TTP, as in systemic lupus erythematosus.

Adult↗

Is lymphoplasmacytic lymphoma/immunocytoma a distinct entity? A clinicopathologic study of 20 cases.

Lymphoplasmacytic lymphoma/immunocytoma (LLI) was defined initially as a small B-cell lymphoma with plasmacytoid or plasmacytic features. Because other types of small B-cell lymphoma, particularly marginal zone B-cell lymphoma may exhibit plasmacytic differentiation, the revised European-American lymphoma classification and World Health Organization has defined LLI more narrowly to exclude other small B-cell lymphomas. The goal of this study was to reevaluate LLI as a clinicopathologic entity. Twenty cases were selected from 43 previously diagnosed as "small lymphocytic lymphoma, plasmacytoid" or "immunocytoma" from 1985 to 1998. Cases fulfilling the criteria for B-cell small lymphocytic lymphoma, follicular lymphoma, marginal zone B-cell lymphoma, or other types of B-cell lymphoma were excluded. The histopathology and immunoreactivity for CD20, CD79a, CD3, CD43, CD23, CD5, kappa, lambda, and immunoglobulins (Ig's) M, G, and A were reviewed, in addition to available clinical findings. There were 13 men and seven women, with a mean age of 69 years. Five patients had documented Waldenström's macroglobulinemia (WM). Three architectural patterns were observed. Pattern A (seven of 20) showed open sinuses, small follicles, and hemosiderosis; pattern B (four of 20) showed hyperplastic follicles; and pattern C (nine of 20) showed diffuse effacement. Epithelioid histiocytes were prominent in patterns B and C but absent in A. Cytologically, six of 20 were polymorphous with 10% to 40% transformed cells; 14 of 20 were lymphoplasmacytic. Five cases showed minor foci of monocytoid B cells. One case showed a composite histology of LLI and small lymphocytic lymphoma. Amyloid was present in two cases. All cases were CD20 and/or CD79a immunoreactive, with two of 20 positive for CD43. Twelve cases were kappa monoclonal and eight cases were lambda monoclonal. Twelve of 17 cases that could be evaluated were positive for IgM and five were positive for IgG. All cases were negative for CD5 and CD23 with the exception of the one case with a composite histology. Eleven of 20 patients with available follow-up died of disease (median, 48 months), and eight of 20 are alive with disease at a follow-up of 6 months to 2 years. LLI does appear to represent a distinct clinicopathologic entity even though it shows morphologic heterogeneity and overlapping features with marginal zone B-cell lymphoma and small lymphocytic lymphoma. Recognition of LLI is important because the overall prognosis may be worse than for other types of small B-cell lymphomas.

Adult↗

Magnetic resonance imaging of cerebrospinal fluid leak and tamponade effect of blood patch in postdural puncture headache.

This prospective study examined the efficacy of magnetic resonance imaging (MRI) in visualizing cerebrospinal fluid (CSF) leak in patients with postdural puncture headache (PDPH) and determining the spread of the blood patch in the epidural space and the extent of tamponade on the thecal sac. After obtaining institutional review board approval, five patients with symptomatic PDPH after 3 days of failed conservative treatment were included in this study. MRI using proton density (PD) and T2-weighted imaging was performed on all patients and CSF flow studies were done on one patient. All patients received 20 mL of blood in the epidural space. They remained supine for 45 min, and repeat MRI studies were performed. Extent of the spread of blood in the epidural space was measured. A visual analog scale of 0-10 was used to evaluate the headache. All patients had severe postural headache with nausea/vomiting. Preblood patch MRI showed extrathecal CSF and hemosiderosis indicating the site of dural puncture in four patients. The postprocedure MRI demonstrated the blood patch as a large extradural collection with anterior displacement of the thecal sac, the mean spread being 4.6 intervertebral spaces. The tamponade effect of the blood patch was observed on PD, T2-weighted, and CSF flow images. All patients experienced immediate resolution of their symptoms. This study suggests that using MRI, the site of the CSF leak, the tamponade effect of the blood patch, and its spread in the epidural space can be documented.

Adult↗

Rapidly destructive arthropathy of the hip in siblings.

A case of rapidly destructive arthropathy of the hip in male siblings aged 74 and 76 years is reported. Hip joints of the brothers were destroyed 12 and 4 months after the onset of symptoms, respectively. Results of clinical and laboratory examinations did not show any features of neuropathic, inflammatory, or septic arthropathy. Pathologically in both patients, osteoarthrotic changes with small foci of bone necrosis and nonspecific inflammation and moderate amount of hemosiderosis in the synovium were observed.

Aged↗