Long-term efficacy and safety of quadruple therapy in childhood diffuse proliferative lupus nephritis.

In this study, we evaluated the frequency, clinical presentation, treatment protocols, prognostic factors, and outcome in children with diffuse proliferative lupus nephritis (DPLN). Between June 1990 and December 2004, 46 patients were diagnosed to have systemic lupus erythematosus (SLE), and 26 of them (56.5%) were found to have DPLN. Renal manifestations were present in 25 patients, and the majority of them presented with severe renal findings, such as nephrotic syndrome and renal failure. All patients were given a quadruple therapy protocol including 6-12 monthly courses of methyl prednisolone pulse therapy combined with oral prednisolone, oral cyclophosphamide, azathioprine, and dipyridamole. Nineteen of these patients were regularly followed up with a mean follow-up period of 5.9 years. Complete remission was achieved in 15 of 19 patients, and chronic renal failure developed in four patients. Renal survival rate was calculated to be 78.9% at the end of 5, 10, and 14 years. Although nephrotic range proteinuria, hypoalbuminemia, renal failure, and activity index above 12/24 at presentation seemed to be associated with poor prognosis, no significant difference could be found. Hypertension and chronicity index greater than 6/12 were found to be bad prognostic predictors. We concluded that satisfactory results were achieved with our quadruple therapy protocol; thus, more aggressive and expensive therapies can be avoided and preserved for more serious and persistent diseases.

Expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in tissues with a diagnosis of childhood lymphoma.

Matrix metalloproteinases (MMP) are enzymes involved in the reconfiguration of the microenvironment by means of degrading the extracellular matrix and have more than 20 subgroups containing zinc. Proteins that serve as the inhibitors of these enzymes are called tissue inhibitors of matrix metalloproteinase (TIMP). These enzymes have been shown to be active in a wide range of processes, from wound recovery to fetus development, heart diseases, and spread of malignant diseases. The aim of this study was to investigate whether there is a relationship between the type, stage, and prognosis of childhood lymphoma subjects and matrix metalloproteinase type-9 (MMP-9) and its inhibitor, tissue inhibitor of matrix metalloproteinase type-1 (TIMP-1). Paraffin blocks of childhood patients diagnosed with non-Hodgkin lymphoma (n = 23), Hodgkin lymphoma (n = 14), or reactive lymphadenopathy (n = 12) were retrospectively immunohistochemically stained with MMP-9 and TIMP-1 stains and whether there was a relationship between the degree of staining and the type, tumor stage, and prognosis of the disease was investigated. Moderate and high degrees of MMP-9 staining were detected in 94.6% of the lymphoma patient tissues and a slight TIMP-1 staining was detected in 21.6% of the lymphoma patient tissues. No relationship was observed between the degree of these staining patterns and the type, tumor stage, and prognosis of the disease. This study indicates that the equilibrium between MMP-9 and TIMP-1 is important in lymphomas in addition to all the physiological and pathologic events although MMP-9 and the TIMP-1 staining patterns are not related to the tumor stage, prognosis, and type of the disease. Larger series of patients are needed to determine the prognostic value of MMP-9 and TIMP-1 in childhood lymphoma.

Histopathological and ultrastructural effects of glycolic acid on rat skin.

Use of alpha hydroxy acids (AHA) to ameliorate specific dermatological problems with keratinization has become fairly widespread. The aim of this study was to evaluate the effects of the AHA derivative of glycolic acid, applied in different dosages, on rat skin using light and electron microscopy. Skin biopsies were taken from the dorsal side of rats (n=16) and at the end of each week after applying solutions containing AHA: week 1, 8% (n=5); week 2, 50% (n=5); week 3, 70% (n=6). The skin samples were fixed in 10% formalin for histology and 2.5% glutaraldehyde solution for electron microscopy and processed using routine protocols. Histological sections were stained with hematoxylin and eosin (H&E), Masson's trichrome and were also labelled for binding of a primary antibody against collagen I using the avidin-biotin-peroxidase method. The epidermal thicknesses were measured and the fibroblast count of the dermis was taken and the results compared using the statistical ANOVA test. Semi-thin sections were stained with toluidine blue-azure II solution and ultrathin sections were contrasted with uranyl acetate and lead citrate. Histochemical and immunohistochemical observations demonstrated that AHA treatment resulted in statistically significant increased thickness of the epidermis and an increase in numbers of active fibroblasts and in the amount of dense collagen, especially at higher dosages of AHA. Ultrastructural examination of rat skin from AHA-treated groups showed cytoplasmic vacuolization in epidermal keratinocytes, intercellular dysjunctions, and increased quantities of organized bundles of collagen fibers in the dermis. The use of AHA in appropriate dosages has been found to play an important role in the treatment of specific skin disorders, however, the harmful effects of use of AHAs at higher concentrations should not be ignored. We conclude that alpha hydroxyl acids have a wide spectrum of use in the field of dermatology but, due to side-effects, their use, dosage, and time frame should be restricted to the advice of dermatologists.

Visceral leishmaniasis and pseudomonas septicemia associated with hemophagocytic syndrome and myelodysplasia in a Turkish child.

An 18-month-old boy presented with fever, hepatosplenomegaly, jaundice, pancytopenia, hyperferritinemia, hypertriglyceridemia and evidence of hemophagocytosis and trilineage myelodysplasia in the bone marrow aspiration. Appropriate treatment was begun but he died after 12 hours of hospitalization due to Gram-negative septicemia. Post-mortem examination of liver biopsy revealed diffuse hemaphagocytic lymphohistiocytosis and Leishmania-donovani bodies in macrophages.

A one-center experience with pediatric percutaneous renal biopsy and histopathology in Ankara, Turkey.

In this study we evaluated the indications, complications, and the spectrum of histopathological results of percutaneous renal needle biopsy (PRNB) performed in our clinic. Between June 1990 and December 2006, 679 PRNBs were performed on native kidneys of 614 children (304 boys, 310 girls) with a mean age of 10.4 years. Most frequent indications for PRNB were nephrotic syndrome (47%), hematuria, and/or proteinuria (15.9%), acute renal failure (14.6%) and complex renal manifestations (18.9%). The overall complication rate was 15.2%. The most common complications were perirenal hematoma (12.4%) and macroscopic hematuria (2.6%). The most frequent histopathological group of diseases were glomerulopathies; these were diagnosed in 376 patients (61.2%) and included membranoproliferative glomerulonephritis (11.1%), mesangial proliferation (10.7%), diffuse proliferative glomerulonephritis (7.7%), and focal segmental glomerulosclerosis (7.3%) as the most frequent. The second most frequent group of histopathology was manifestations secondary to systemic diseases; these were shown in 195 patients (31.8%). Amyloidosis (11.4%) and Henoch-Schönlein nephritis (9.9%) made the majority of this group. In conclusion, our study demonstrated that PRNB is a safe procedure with usually transient complications showing the most frequent renal diseases that cause diagnostic and therapeutic difficulties for pediatric nephrologists.

Acute renal failure due to rhabdomyolysis in a child with McArdle disease.

Rhabdomyolysis induced acute renal failure (ARF) is relatively rare in children. We report an 8-year-old boy with McArdle disease and rhabdomyolysis induced ARF after heavy muscle work. Physical examination revealed generalized tenderness on his extremities. Laboratory examinations showed acute renal failure due to myoglobinuria and revealed alanine transaminase 428 U/l, aspartate transaminase 1,400 U/l, blood urea nitrogen 119 mg/dl, creatinin 3.6 mg/dl, uric acid 13 mg/dl, and serum creatinine kinase (CK) 33,766 U/l. Hemodialysis was carried out for ARF. His clinical and laboratory findings improved and became normal in 2 weeks. Enzymatic analysis of the muscle biopsy showed a phosphorylase A level of 129 nmol/s/mg protein (normal: 200-600) and a phosphorylase A+B level of 385 nmol/s/mg protein (normal: 500-1500), which was compatible with glycogenosis type V. As McArdle disease rarely becomes symptomatic and ARF secondary to this condition is very rare, our case represents a rare clinical presentation.