Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis worldwide, and the renal biopsy is the gold standard for establishing the diagnosis. Although the prognostic value of the renal biopsy in ANCA-associated glomerulonephritis is widely recognized, there is no consensus regarding its pathologic classification. We present here such a pathologic classification developed by an international working group of renal pathologists. Our classification proposes four general categories of lesions: Focal, crescentic, mixed, and sclerotic. To determine whether these lesions have predictive value for renal outcome, we performed a validation study on 100 biopsies from patients with clinically and histologically confirmed ANCA-associated glomerulonephritis. Two independent pathologists, blinded to patient data, scored all biopsies according to a standardized protocol. Results show that the proposed classification system is of prognostic value for 1- and 5-year renal outcomes. We believe this pathologic classification will aid in the prognostication of patients at the time of diagnosis and facilitate uniform reporting between centers. This classification at some point might also provide means to guide therapy.
Intracellular changes in enzyme activity and the isoform pattern of protein kinase C (PKC) during treatment with doxorubicin (DXR) were examined in a rat ascites hepatoma AH66 parental cell line (AH66P), which shows slight expression of P-glycoprotein (Pgp) on the cell membrane and is classified as an intrinsic multidrug-resistant cell. AH66P cells, treated for 10 days with DXR at the concentrations of 0.3 or 5.0 muM, exhibited moderate to severe inhibition of PKC activity after transient increase of the activity, which mainly was either Ca2+-independent and phospholipid-dependent or Ca2+-independent and phospholipid-independent. PKC isoform analysis of the treated cells also indicated the transient 1.5- and 1.8-fold increase of PKC-delta and PKC-zeta as well as slight increase of PKC-alpha in treatment with 0.3 muM DXR and 1.9- and 1.6-fold increase of PKC-alpha and PKC-zeta with slight increase of PKC-delta in treatment with 5.0 muM, respectively. A small, but interesting discrepancy between the markedly elevated enzyme activity, which was composed particularly of both cofactor-independent forms, and the relatively low levels of isoform expression, was found when the cells were treated with 5.0 muM DXR. It is of great interest that DXR-treatment, while only slight increasing P-glycoprotein (Pgp) phosphorylation, enhanced the transient expression of Pgp on the cell membrane with good correlation with the fluctuating change in PKC activity. These results indicate that the possible expression of some or novel specific isoform(s) of PKC may modulate and be associated with expression of the Pgp.
AbstractBackground: Neural epidermal growth factor-like 1 protein (NELL1) is a target antigen of membranous nephropathy (MN). NELL1-associated MN (NELL1-MN) was originally a primary form but has been associated with other diseases, including malignancies, pre-exposure to certain drugs, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and rheumatoid arthritis (RA). Case presentation: A 78-year-old woman with long-standing RA developed persistent proteinuria and was diagnosed with MN. Evaluation of the underlying cause revealed chronic active HCV infection and past HBV infection. The underlying cause was less likely to be drug-related; however, there was no evidence of malignancy. The patient was diagnosed with HCV-associated MN. At 4 years after MN diagnosis, the patient died of breast cancer with multiple metastases. Subsequent immunohistological analysis revealed that she had NELL1-MN and that her breast cancer tissue positively stained for NELL1. Conclusions: Our case illustrates the difficulty in establishing the underlying disease of NELL1-MN, even after diagnosis. However, the incidence of malignancies, particularly breast and prostate cancers, is higher in NELL1-MN than in MN with other target antigens. Therefore, malignancies are considered a priority for investigation because of their frequency and prognosis among patients with NELL1-MN.
Fundamental and clinical studies were carried out on cefixime (CFIX) 5% granules, and the results are summarized below. Antimicrobial activity Antimicrobial activities of CFIX, cefaclor, cefroxadine, cephalexin and amoxicillin (AMPC) were studied against clinical isolates. CFIX showed greater activities than all the other antibiotics against E. coli, K. pneumoniae, H. influenzae, P. mirabilis, E. cloacae and S. marcescens, but it was slightly less active than AMPC against S. pyogenes. Absorption and excretion Serum concentrations and urinary excretions of CFIX were determined following single or repeated oral administration. In 8 patients given single dose of CFIX 1.5 or 3.0 mg/kg, mean serum concentrations were 1.27 and 1.09 micrograms/ml at 2 hours, 1.27 and 1.35 micrograms/ml at 4 hours, 0.85 and 1.10 micrograms/ml at 6 hours, 0.17 and 0.24 micrograms/ml 12 hours after administration, respectively. Mean serum half-lives were 2.54 hours for the dose of 1.5 mg/kg and 2.60 hours for 3.0 mg/kg. Urinary recovery rates in the 12-hours urine varied 6.7 to 33.6%, with an average of 13.5%. In 3 patients given a repeated dose of CFIX 3.0 or 5.6 mg/kg b.i.d., the serum concentrations were 0.23-1.01 micrograms/ml at 0 hour, 1.91-2.80 micrograms/ml at 2-4 hours and 1.13-2.07 micrograms/ml at 6-8 hours after administration. Clinical study The CFIX was given orally by mainly b.i.d. at a daily dose of 4.4-11.6 mg/kg for 4-15 days to a total of 33 patients consisting of 3 patients with pneumonia, 3 with bronchitis, 9 with tonsillitis, 15 with UTI, one each with scarlet fever, lymphadenitis and colitis. Clinical responses were excellent in 24 patients, good in 8 and fair in 1, with an effectiveness rate of 97.0%. All of the 21 bacterial isolates examined were eradicated after CFIX treatments including 3 beta-lactamase producing strains. No side effects of abnormal laboratory findings were observed in these patients.
In the period 1985 to 1993, a total of 802 school-aged children (284 first-graders and 518 seventh-graders) were referred to our hospital for further evaluation of electrocardiographic abnormalities. Among them, 57 (male 24 and female 33) children were confirmed as having Wolff-Parkinson-White (WPW) syndrome based on the findings of 12-lead surface electrocardiograms (ECG). According to Lindsay's criteria, the locations of the accessory pathways were as follows: Left-lateral in 10 (18%), left-posterior in 2 (4%), right-free-wall in 28 (49%), anterior-septum in 13 (23%) and posterior-septum in 3 (5%). One 12-y-old girl had multiple accessory pathways. Six patients had associated diseases: Ebstein's anomaly in 4, epilepsy in 1 and mental retardation with scoliosis in 1. Follow-up periods ranged from 2.0 to 13.0 y (mean +/- SD: 8.0 +/- 3.3 y) for 23 first-graders with WPW syndrome, and from 2.0 to 13.0y (mean +/- SD: 7.3 +/- 4.2y) for 34 seventh-graders, respectively. Initially, 5 children had at least one episode of supraventricular tachycardia (SVT) by history and 6 children developed SVT during the follow-up. One girl with multiple accessory pathways and recurrent SVT required long-term drug therapy.The outcome of children with WPW syndrome detected by a heart screening program at school was favorable. Our 8 y follow-up of 57 children with WPW syndrome will serve as additional information concerning the indication of radio-frequency catheter ablation therapy for WPW syndrome in children.
