Multiple intramedullary lipomas with conal intramedullary dermoid: magnetic resonance appearances.

BACKGROUND CONTEXT: Intramedullary fat-containing benign childhood tumors of the cord include lipomas, dermoid cysts, and teratomas. These are embryonal tumors. Most intramedullary fat-containing tumors are solitary. Multiple intramedullary lipomas are rare and may represent a spinal lipomatous malformation. The presence of another intramedullary dermoid tumor in the same case is rare. PURPOSE: The intent of this case report is to look at magnetic resonance features and possible mechanisms of association of these fat-containing intramedullary tumors. STUDY DESIGN/SETTING: A 3-year-old male child presented with spastic quadriplegia. METHODS: Magnetic resonance imaging (MRI) of spine was done on a 1.5-T scanner in different planes. RESULTS: MRI showed multiple intramedullary spinal lipomas with an intramedullary dermoid involving the conus, cord atrophy, and subarachnoid fat droplets. CONCLUSION: Multiple intramedullary lipomas with an intramedullary dermoid represent a form of spinal lipomatous malformation. Both may represent embryogenic mesenchymal inclusions and hamartomatous growth, which can be accurately diagnosed with MRI.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

The estimation of the plasma free fraction of cyclosporine in rabbits and heart transplant patients: The application of a physiological model of renal clearance

We estimated the free fraction (f_u) of cyclosporine (CyA) in the plasma from concentrations of CyA in urine (C_u) and plasma (C_p), urine flow rate (UF), and glomerular filtration rate in rabbits and in heart transplant patients. Following intravenous administration of CyA (5–30 mg kg^?1) in ten NZW rabbits and oral administration of CyA (4.8–12.1 mg kg^?1) in nine heart transplant patients, CyA concentrations in urine and plasma were measured by HPLC. The ratios of C_u to C_p and UF data were fitted to a physiological model of renal clearance using NONMEM. The free fraction of cyclosporine in the rabbits and the heart transplant patients was 0.0122 and 0.14, respectively. Because of the relatively low permeability of CyA across the tubular epithelium, no apparent equilibrium between C_u and C_p at any urine flow rate was reached and, therefore, the C_u to C_p ratio will not be equal to f_u.     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome

 Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules. Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was  – 0.05 ± 0.16, and in MCNS  – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS (P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with heavy proteinuria compared with children with MCNS with heavy proteinuria. Received August 7, 1996; received in revised form and accepted December 16, 1996     

Levels, Complement Activity and Polymorphisms of Mannan-Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis

Activation of complement pathways, leading to production of C3a and C5a anaphylatoxins, has been postulated in the pathogenesis of asthma and allergic airway inflammation. The present study was undertaken to investigate the role of mannan-binding lectin (MBL), an initiator of the lectin pathway of complement, in asthma and allergic rhinitis. MBL levels and MBL-induced complement activity were determined in 19 patients of bronchial asthma with allergic rhinitis and 20 unrelated, age-matched controls of Indian origin. MBL levels and activity were correlated with percent eosinophilia and percent predicted FEV1 values of the patients. Association of single nucleotide polymorphisms (SNPs) in exon 1 and intron 1 of the MBL with the disease, clinical markers, MBL levels and MBL-induced complement activity was analysed using standard statistical tools. Significantly higher MBL levels and activity were observed in patients of bronchial asthma with allergic rhinitis as compared to the controls. We identified five SNPs, of which two, A816G in exon 1 and G1011A in intron 1 of the MBL, were novel. SNP G1011A was significantly associated with the disease ( P =  0.0024, OR = 5.8696, 95% CI: 1.7316 < OR < 19.8963). Individuals with 'A' allele at position 1011 showed increased MBL levels, activity and disease severity. Our results suggest that 'A' allele at position 1011 leading to high MBL levels and complement activity may be contributing to the severity of bronchial asthma and allergic airway inflammation.