Autoimmune hepatitis associated with the odour of fish food proteins: a causal relationship or just a mere association?

We present the case of a 15-year-old boy [HLA phenotype: A 1, 25 (10); B 18, 8; C 7; DR 17 (3), 6] with classic (type 1) autoimmune hepatitis presumably caused by a long-term exposure to the strong odour of food fed to a large number of tropical fish which that the boy kept in tanks in his bedroom. The boy presented with a history of recent symptoms of common cold, and a high cytomegalovirus-IgG titer, both known to activate proinflammatory cytokines. The patient's laboratory results and physical findings improved without specific treatment during his first stay in the hospital for several weeks, as well as when the thanks were removed from his bedroom while disease activity increased after his return home. This suggests that the association with fish food odour (putative volatile protein antigens) was not simply coincidental. Our patien's history is in agreement with the recently postulated pathomechanism of autoimmune hepatitis, according to which viral infections may trigger the disease in a genetically predisposed individuals persistently exposed to a constant antigenic stimulus, which results in ongoing allergic inflammation and finally develops into an immune process. The spontaneous remissions observed in our patient were characteristic of the natural course of autoimmune hepatitis and may reflect periods when he was not exposed to the eventually harmful effects of the odour of fish food proteins.

Autoimmune hepatitis associated with the odour of a fish food proteins: a causal relationship or just a mere association?

We present the case of a 15-year-old boy [HLA phenotype: A 1, 25 (10); B 18, 8; C 7; DR 17 (3), 6] with classic (type 1) autoimmune hepatitis presumably caused by a long-term exposure to the strong odour of food fed to a large number of tropical fish which that the boy kept in tanks in his bedroom. The boy presented with a history of recent symptoms of common cold, and a high cytomegalovirus-IgG titer, both known to activate proinflammatory cytokines. The patient's laboratory results and physical findings improved without specific treatment during his first stay in the hospital for several weeks, as well as when the thanks were removed from his bedroom while disease activity increased after his return home. This suggests that the association with fish food odour (putative volatile protein antigens) was not simply coincidental. Our patien's history is in agreement with the recently postulated pathomechanism of autoimmune hepatitis, according to which viral infections may trigger the disease in a genetically predisposed individuals persistently exposed to a constant antigenic stimulus, which results in ongoing allergic inflammation and finally develops into an immune process. The spontaneous remissions observed in our patient were characteristic of the natural course of autoimmune hepatitis and may reflect periods when he was not exposed to the eventually harmful effects of the odour of fish food proteins (AU)

Se presenta a un paciente de 15 años [fenotipo de HLA: A 1, 25 (10); B 18, 8; C 7; DR 17 (3), 6] con hepatitis autoimnune clásica (tipo 1) probablemente causada por la exposición a largo plazo al intenso olor de alimentos destinados a un gran número de peces tropicales que el chico guardaba en tanques en su dormitorio. Existían antecedentes de síntomas recientes de catarro y un título elevado de IgG por infección por citomegalovirus (IgG-CMV), factores ambos que activan citocinas proinflamatorias. La aparente mejoría de los resultados analíticos del paciente y de los hallazgos físicos sin tratamiento específico durante su primera estancia hospitalaria a lo largo de varias semanas (y también cuando se retiraron los tanques del dormitorio) podría indicar que la asociación de los síntomas al olor de una comida para peces (supuestos antígenos proteicos volátiles) no fue simplemente casual. La historia de nuestro paciente concuerda con el patomecanismo propuesto recientemente de hepatitis autoinmune en el que las infecciones virales pueden desencadenar la enfermedad en un paciente predispuesto genéticamente y expuesto de forma persistente a una estimulación antigénica constante que produce una inflamación alérgica progresiva que, finalmente, se desarrolla como un proceso inmunitario. Las remisiones espontáneas observadas en nuestro paciente eran características de la evolución natural de la hepatitis autoinmune y podría reflejar períodos en los que no estuvo expuesto a los posibles efectos perjudiciales del olor de las proteínas de los alimentos para peces (AU)

Clinical pharmacology of furosemide in children: a supplement.

Furosemide is one of the most effective and least toxic diuretics used in pediatric practice. Experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in its diuretic effect. Also, the drug appears to have anti-inflammatory properties. In children with different diseases who received orally or intravenously 1 to 2 mg/kg doses of furosemide, a statistically significant positive linear relationship was found between the drug urinary excretion rate and the urine flow rate, but log dose-response curves to the drug were found to vary depending on the disease and the route of the drug administration. No sigmoid-shaped log dose-response curve (ie, one approaching a zero response at very low furosemide urinary excretion rates and a maximum response at very high excretion rates) was attained, which may suggest that the capacity of the kidney tubules to respond diuretically to the aforementioned doses of furosemide was not exceeded in these patients. However, in infants with different diseases and reasonably normal renal function who required administration of this diuretic, a very steep log dose-response curve to a 1 mg/kg intravenous dose of furosemide was found, which may suggest that higher doses may not result in a significant increase in diuretic response. The lowest mean furosemide urinary excretion rate and its concentration in urine associated with a significant diuresis were found to be 0.58 +/- 0.33 microg/kg/min and 24.2 +/- 10.5 microg/ml, respectively. Also, a significant correlation was found between the amount (in milligrams) of furosemide excreted in the urine during the first 6 hours after administration and the urine volume collected during that time. Patients with cystic fibrosis appeared to have a markedly more pronounced diuretic response to the average oral dose of 0.835 +/- 0.18 mg/kg than that reported in control children given 2 mg/kg. In children with acute renal failure caused by acute gastroenterocolitis or glomerulonephritis, a broad relationship was observed between a single intravenous dose and diuretic response after administration of furosemide (1.2 to 30.8 mg/kg). It was suggested that the total daily dose of the drug should not exceed 100 mg in these patients. Furosemide was found to be effective in management of bronchoconstriction accompanying chronic lung disease and narrowing of the upper respiratory airways; in hydrocephalus in infancy to avoid cerebrospinal fluid shunts; in some diagnostic procedures, such as an assessment of fetal and neonatal hydronephrosis; and in evaluation of different types of renal tubular acidosis. Among side effects accompanying clinical use of this drug were cholelithiasis in premature infants receiving total parenteral nutrition concomitantly with the diuretic; secondary hyperparathyroidism and bone disease in infants obtaining long-term furosemide treatment; and drug-induced fever.

Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report.

Neutrophil-derived proteinases cause glomerular injury by proteolysis of the glomerular basement membrane and alterations in glomerular metabolism. Recently, a marked elevation of the plasma elastase complex with alpha1-proteinase inhibitor (alpha 1-PI) both in the acute phase and during remission of nephrotic syndrome (NS) compared with age-matched controls was reported. In experimental immune-mediated glomerulonephritis epsilon-aminocaproic acid (EACA) significantly reduced albuminuria, and it was suggested that this may be linked with the antiproteolytic activity of the drug. We studied plasma antithrombin III (AT-III), alpha 1-PI, alpha 2-antiplasmin (alpha 2-A), alpha 2-macroglobulin (alpha 2-M) activity, and some blood coagulation and fibrinolysis tests in children with frequently relapsing prednisone-responsive NS. Also, the effect of prednisone alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment regimens on the studied parameters was estimated. All investigations were performed on admission to the hospital and after approximately 13 days of prednisone alone therapy (Group I), as well as before the administration of prednisone plus EACA and 24 hours after the last dose of EACA, ie, after approximately 5 days of treatment (Group II). Prednisone was administered at the usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of disease, NS patients (n = 19) were shown to have a statistically significant decrease of plasma AT-III (16.4 +/- 4.7 vs. 21.9 +/- 2.5 IU/mL) and alpha 1-PI (1.28 +/- 0.6 vs. 1.97 +/- 0.34 IU/mL) activity, as well as a marked increase in plasma alpha 2-M activity (14.96 +/- 5.81 vs. 9.6 +/- 1.6 IU/mL), and fibrinogen concentration (5.51 +/- 1.78 vs. 2.96 +/- 0.34 g/L) compared to the age-matched controls; no significant changes in plasma alpha 2-A activity, plasminogen concentration, euglobulin clot lysis time, activated partial thromboplastin time (APTT), or thromboplastin time were noted. In children treated with prednisone alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and alpha 2-A (36%, P < 0.019) activity, and a significant decrease of the plasma fibrinogen concentration (6.07 +/- 1.66 vs. 3.17 +/- 1.64 g/L, P < 0.001), and APTT (45.1 +/- 7.6 vs. 33.8 +/- 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003), whereas plasma fibrinogen concentration and APTT remained unchanged. However, statistically significant differences between the pre- and posttreatment plasma AT-III, alpha 1-PI, and alpha 2-A activities in these patients were observed. There was also a relationship between EACA dose and the percentage change in plasma alpha 2-A activity. In a few patients receiving prednisone plus EACA regimen, side effects that included purulent rhinitis, pharyngitis, increases in body temperature, loose stools, and an approximately 20% to 30% decrease in systolic and diastolic arterial blood pressure were observed. Thus, although the prednisone plus EACA treatment regimen seems to offer new therapeutic possibilities in some patients with NS, it should not be used in acute phase of the disease.

Impaired activation of the fibrinolytic system in children with Henoch-Schönlein purpura: beneficial effect of hydrocortisone plus Sigma-aminocaproic acid therapy on disappearance rate of cutaneous vasculitis and fibrinolysis.

Systemic vasculitis is a predominant clinical symptom in Henoch-Schönlein purpura (HSP), and some studies suggested that decreased blood fibrinolytic activity, as well as blood platelets, is of importance in the development of cutaneous vasculitis. Although patients with HSP have normal blood coagulation, little is known about the fibrinolytic system. On the other hand, it is known that the focus of Sigma-aminocaproic acid (EACA) activity in vivo is probably the blood platelet-vessel wall interaction or a vascular component alone. The aim of this study was, therefore, to investigate blood coagulation and fibrinolytic system as well as the effect of hydrocortisone (H) plus EACA therapy (Group I) on plasma antithrombin-III (AT-III), alpha1-proteinase inhibitor (alpha1-PI), alpha2-antiplasmin (alpha2-A), alpha2-macroglobulin (alpha2-M) activity, fibrinogen and plasminogen concentrations in plasma, euglobulin clot lysis time (ELT), and disappearance rate of cutaneous vasculitis in 14 children with HSP aged 7.6 +/- 3.1 (SD) years. Ten patients (8.6 +/- 2.5 years old) were treated with H alone (Group II), and 8 healthy, age-matched children served as controls. Plasma proteinase inhibitor activity was estimated with the kinetic method using Boehringer chromozyme tests before administration of H (9.2 +/- 3.3 mg/kg/d, i.v.) plus EACA (140 +/- 52 mg/kg/d, p.o.) for 5.93 +/- 2.05 days, and 24 hours after the last dose of EACA, as well as before and after treatment with H alone (8.25 +/- 1.74 mg/kg/24 h, i.v.) for 7.1 +/- 1.2 days. It was found that patients with HSP had the initial fibrinogen and plasminogen plasma concentrations significantly increased compared with the controls (Group I: 3.93 +/- 1.3 g/L and 124 +/- 38%; Group II: 4.24 +/- 0.89 g/L and 134 +/- 42% vs. 2.96 +/- 0.34 g/L, and 90 +/- 14%, respectively). Also, there was a marked decrease of the initial plasma alpha2-A activity in Group II compared with the controls (0.69 +/- 0.29 vs. 0.94 +/- 0.11 IU/mL, respectively, t = 2.33, P <.045). Both treatment regimens significantly improved fibrinolysis, which manifested as a shortening of ELT, but the mean values of this parameter remained within normal range. After treatment with H plus EACA, the skin lesions started to disappear significantly faster compared with the H alone regimen (2.28 +/- 0.45 days vs. 4.12 +/- 1.05, t = 4.41, P <.0023). In four of six patients receiving H plus EACA therapy, an approximately 20% decrease of systolic and diastolic arterial blood pressure lasting for 5 to 7 hours after administration of EACA was observed. These results may suggest that children with HSP have impaired plasma fibrinolytic activity and that an increased release of plasminogen activator inhibitor-1 (PAI-1) might be, at least in part, responsible for this phenomenon. Concomitant use of H (approximately 10 mg/kg/d) plus EACA (approximately 100 mg/kg/d) for a few days opens new therapeutic possibilities in some children with HSP.

[Urinary tract infections in children]. / Zakazenia ukladu moczowego u dzieci.

The advances in definition, pathogenesis, diagnosis and treatment of urinary tract infections (UTI) in children have been presented. The mechanism of UTI and predisposing factors related to host and bacteria, problems in evaluating of UTI with the use of fresh urine microscopy for the presence of leukocytes, utility and reliability of ultrasonography, intravenous urography, contrast micturating cystourethrography, and technetium-99m dimercaptosuccinic acid renoscintigraphy studies were discussed. Differences in clinical symptoms and treatment of acute and chronic phase of UTI with oral and intravenous antibiotics and other drugs depending on the age of a patient, management of asymptomatic bacteriuria, side effects of drugs, as well as prophylaxis, were reported.

[Favorable effects of epsilon-aminocaproic acid on the children with nephrotic syndrome and Schonlein-Henoch syndrome treated with corticosteroids]. / Korzystny wplyw kwasu epsilon-aminokapronowego u dzieci chorych na zespól nerczycowy i zespól Schönleina-Henocha leczonych kortykosteroidami.

An effect of EACA given in the daily dose of 85-230 mg/kg for 1-1-days on the activity of certain plasma protease inhibitors in 7 children with steroid-sensitive and steroid-dependent nephrotic syndrome (age between 3.5 and 18 years), and in 6 children with Schönlein-Henoch syndrome (aged between 3.5 and 6 years). Additionally, an effect of EACA on clinical status, dynamics of improvement, proteinuria and/or erythrocyturia, and incidence of adverse reactions was studied. It was found that EACA significantly increased antithrombin III activity by approximately 68.8% proteinase alpha 1-inhibitor by 41.8% alpha 2-antiplasmin by 55% in patients with nephrotic syndrome, and increased an activity of protease alpha 1-inhibitor by 75% in patients with Schönlein-Henoch syndrome. EACA given together with corticosteroids enhanced their efficiency manifested--especially in children with Schönlein-Henoch syndrome--by a rapid diminishment of skin changes, proteinuria and erythrocyturia. A drop in blood pressure, loose stools, upper respiratory inflammation, and fever were most frequent adverse reactions. EACA given alone produced rapidly increasing edema in patients with hephrotic syndrome. It seems that EACA may be used as an adjuvant therapy in some cases of nephrotic and Schönlein-Henoch syndromse.

[Orthopedic foot abnormalities as a important sign of lumbosacral spinal lipoma in an 11-year-old boy]. / Nieprawidlowosci ortopedyczne stopy jako objaw tluszczaka odcinka ledzwiowo-krzyzowego kanalu kregowego u 11-letniego chlopca.

A case of an 11-year-old boy with giant lumbosacral spinal lipoma is presented. Hobbling on the left foot and its dropping was observed at the age of 9 after which left equinovarus foot and excavated foot deformities developed. Diurnal and nocturnal enuresis, infection of the urinary tract, and bilateral vesico-ureteral reflux were found. At birth, the patient had cleft palate and cleft upper lip, and bending of the interbuttocks groove, which is suggestive of occult spina bifida. It seems that in the case of orthopedic foot abnormalities developing in a previously healthy child, MRI investigation of the lumbosacral spine should be considered.

Urographic percentile charts for vertical kidney mobility in childhood.

Vertical kidney mobility was measured in excretory urograms in 492 children of both sexes, 1 to 16 years of age. The positions of the lower poles of the kidneys were compared in radiographs taken in recumbent and erect children. The mean values and standard deviations of the mobility were calculated (in mm) in 15 one-year-age subgroups, body weight subgroups (intersubgroup difference = 5 kg) and in the lumbar segment L1-L4 length subgroups (intersubgroup difference = 5 mm), establishing the limiting values including 3, 10, 25, 50, 75, 90 and 97% of the studied population of boys and girls. It was found that in the group aged 15-16 years, the mobility of the right kidney was greater than that of the left kidney both in boys and girls. With increasing body weight the mobility of both kidneys corresponding to the 97th centile increased in boys, while in girls the mobility of the right kidney decreased when the body weight of 60-70 kg was reached, and that of the left kidney decreased after reaching 50-60 kg. In boys with the increase in length of the lumbar segment L1-L4, the mobility values corresponding to the 97th centile were markedly increased. The obtained percentile charts of vertical kidney mobility in children will be useful when nephropexy is to be performed.

[Immunologic state and effect of long-term levamisole therapy on selected immunologic parameters in children with steroid sensitive nephrotic syndrome during remission]. / Stan immunologiczny i odlegly wplyw lewamizolu na niektóre parametry immunologiczne u dzieci chorych na sterydowrazliwy zespól nerczycowy w okresie remisji.

Immunological system was tested in 14 children aged between 1.5 and 14 years (mean 5.4 years) with steroid-sensitive nephrotic syndrome during remission. Levamisole (Decaris Richter) was administered in the dose of 2-3.5 mg/kg twice a week for 2.5-6 months. Immunological tests carried out before treatment showed a decrease in total T-cells and T2 subpopulation in 78.6% of patients in comparison with normal values for this age group; a decrease in total B-cells was noted in 87.6% of patients, and percentage of these cells was decreased on 57.1% of cases; gamma-globulins in blood serum were decreased below lower normal values in all children whereas serum IgM levels were above the upper limit of the normal values. Therapy with levamisole normalized total T-cells in 91.7% of patients (p < .05) mainly due to an increase in the number of T1 cells (by 127% in 7 patients in comparison with baseline values considered as 100%); total number of B-cells reached the values normal for this age group in 83.1% of patients (< .05) while percentage of these cells normalized in 66.7% of patients (p < .05), increasing by mean 66.7% in 6 children. It seems that immunologic status of patients with steroid-sensitive nephrotic syndrome during remission depends, at least partially, on the recurrent respiratory tract infections and/or urinary tract infections accompanying the underlying disease. No significant levamisole effect on blood SGOT, SGPT, platelet count and leucocytosis was noted.

[A case of histiocytosis of Langerhans cells]. / Przypadek histiocytozy komórek Langerhansa.

A lethal case is presented of disseminated for of histiocytosis of Langerhans cells in 16-month-old girl. In the clinical course predominated high fever, opportunistic infections, cell-mediated and humoral immunity disturbances, and gross hepatocellular damage which made impossible carrying out of the treatment with cytostatics. The advances in immunological investigations in these patients are more widely discussed as well as the use of thymus hormones.

Pharmacokinetic, biliary excretion, and metabolic studies of 14C-furosemide in the rat.

1. Partition of furosemide into organic solvents at pH 3.8 was greatest for ethyl acetate (33:1) greater than 2-ethyl-1-hexanol (10:1) greater than ethyl ether (6:1). 2. Furosemide was highly bound to human, bovine, rabbit, and rat plasma or albumin (97.4-98.4%). 3. Furosemide was highly bound to rat tissues. One hour after i.p. injection of the drug, tissue to plasma concentration ratios were: adrenals (10:1), lung (4:1), kidney (4:1), spleen (3:1). 4. In rats with ligated renal pedicles, furosemide was excreted in bile, at least in part, by active transport. Hepatic clearance of a 1 mg/kg i.v. dose contributed 20% to total body clearance. Large doses (50 mg/kg and more) of furosemide exerted a choleretic effect. 5. Chromatography of bile showed that i.v. administration of 50 mg/kg and higher doses of furosemide to rats resulted in saturation of hepatic drug metabolism. 6. The bile of rats contained the parent drug, 4-chloro-5-sulphamoyl-anthranilic acid, and at least two unknown metabolites with the furan ring intact.

High doses of furosemide in children with acute renal failure. A preliminary retrospective study.

The diuretic effect of high doses of furosemide alone and furosemide plus mannitol was analysed retrospectively in 30 children with acute renal failure. In 10 children (Group 1) renal failure developed mainly during glomerulonephritis, and in 20 children (Group 2) the cause was gastroenteritis. The diuretic effects of furosemide and furosemide plus mannitol were evaluated measuring the 24-hour urine volume at the time of anuria, oliguria or normal diuresis. The highest mean single intravenous doses of furosemide were 6.5 and 14 mg/kg in Groups 1 and 2, respectively; the highest average daily doses were 10.1 and 25.5 mg/kg, respectively. A broad relationship was observed between single i.v. dose and diuretic response following administration of furosemide (1.2 to 30.8 mg/kg). In both groups of patients a statistically significant negative linear correlation was found between the daily intravenous dose of furosemide and the 24-hour urine volume. Calculations based on the obtained regression equations showed that the expected 24-hour urine volumes corresponding to daily diuresis normal for age could be obtained after administration of daily 2.8 to 1.4 mg/kg furosemide in Group 1 and 9.3 to 2.3 in Group 2. It is therefore suggested that the total daily dose of furosemide should not exceed 100 mg in children with acute renal failure. Administration of furosemide plus mannitol did not result in higher daily diuresis as compared to 24-hour urine volume obtained when furosemide was given alone. Furosemide was well tolerated. Electrolyte disturbances, especially in Group 2, were the most frequent side effects due to high doses of furosemide.

Diuretic effect and disposition of furosemide in cystic fibrosis.

The pharmacodynamics and kinetics of single oral and intravenous doses of furosemide were studied in 9 patients (mean age 18.5 y) with cystic fibrosis. The diuretic effect of furosemide lasted for 6 h after oral administration and 2 h following intravenous injection of the drug. The patients with cystic fibrosis had a more pronounced diuretic response both to the oral and intravenous treatments than that reported in normals. Furosemide caused a marked decrease in urine pH for 5 h following the oral dose and between the 2nd and 3rd h after i.v. injection. The baseline nocturnal urine flow rate in 7 of the 9 patients given furosemide orally was increased by 30.6% compared to that reported in healthy subjects. The bioavailability of furosemide, its mean absorption rate and the mean plasma and urinary elimination half-lives both of the oral and the intravenous drug were similar to those reported in normal subjects. The patients with cystic fibrosis showed, however, about double normal mean total clearance after both the oral and i.v. treatments, and its renal clearance was almost half the plasma clearance. Nonrenal clearance was markedly increased in the patients, which agreed with a considerable decrease in the renal excretion of the drug. The mean apparent volume of distribution was also markedly increased compared to data in the literature. Oral furosemide resulted in a moderate increase in haematocrit and haemoglobin levels in 7 of 9 patients with cystic fibrosis and marked hypokalemia developed in 6 of the 9 patients 6 h after dosing. Pulmonary function tests performed at that time were changed in an inconsistent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

[Administration of levamisole to children with kidney disease exacerbation caused by recurrent respiratory infections]. / Stosowanie lewamizolu u dzieci z zaostrzeniami chorób nerek spowodowanymi nawracajacymi zakazeniami dróg oddechowych.

Levamisole (2.1-3.1 mg/kg twice a week) was administered to 6 children aged between 20 months and 6.5 years for 1 to 4 months. All children suffered form the renal diseases exacerbation (nephrotic syndrome and pyelonephritis--2 children, lipoid nephrosis and pyelonephritis--2 children, pyelonephritis with glomerular reactions--1 child, recurrent pyelonephritis--1 child) due to recurrent respiratory infections levamisole improved both clinical and biochemical parameters of renal disease. Subsequent respiratory infections were milder and less frequent. Transient decrease in thrombocyte count was seen in 4 children after 2-8 weeks of therapy with levamisole. An increase in AspAT and (or) AlAT was noted in 2 children after 1-2 months of therapy. Levamisole was withdrawn in 2 children after 30 days due to an increase in AspAT activity, prolongation of blood clotting time and thrombocytopenia.