Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse: A Noninferiority Randomized Controlled Trial

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Frequent diagnostic errors in cardiac PET/CT due to misregistration of CT attenuation and emission PET images: a definitive analysis of causes, consequences, and corrections.

Cardiac PET combined with CT is rapidly expanding despite artifactual defects and false-positive results due to misregistration of PET and CT attenuation correction data-the frequency, cause, and correction of which remain undetermined. METHODS: Two hundred fifty-nine consecutive patients underwent diagnostic rest-dipyridamole myocardial perfusion PET/CT using (82)Rb, a 16-slice PET/CT scanner, helical CT attenuation correction with breathing and also at end-expiratory breath-hold, and averaged cine CT data during breathing. Misregistration on superimposed PET/CT fusion images was objectively measured in millimeters and correlated with associated quantitative size and severity of PET defects. Misregistration artifacts were defined as PET defects with corresponding misregistration on helical CT-PET fusion images that resolved after correct coregistration using a repeat CT scan, cine CT averaged attenuation during normal breathing, or shifted cine CT data that coregistered with PET data. RESULTS: Misregistration of standard helical CT PET images caused artifactual PET defects in 103 of 259 (40%) patients that were moderate to severe in 59 (23%) (P = 0.0000) and quantitatively normalized on cine or shifted cine CT PET (P = 0.0000). Quantitative misregistration was a powerful predictor of artifact size and severity (P = 0.0000), particularly for transaxial misregistration >6 mm occurring in anterior or lateral areas in 76%, in inferior areas in 16%, and at the apex in 8% of 103 artifactual defects. CONCLUSION: Misregistration of helical CT attenuation and PET emission images causes artifactual defects with false-positive results in 40% of patients that normalize on cine CT PET using averaged CT attenuation data during normal breathing comparable to normal breathing during PET emission scanning and shifting cine CT images to coregister visually with PET.     

p-Amino salicylic acid — oxidized cellulose system: a model for long term drug delivery

The immobilization of p-amino salicylic acid (PASA) on periodic oxidized cellulose (O.C) as a biocompatible carrier was investigated. The immobilization of the PASA is based on Schiff's base formation between the amino group of PASA and the aldehyde group of O.C. The in vivo and in vitro release of p-amino salicylic acid was studied. Such a system may be useful for the sustained delivery of the drugs in the body, since O.C. itself is a biosoluble carrier.     

Alteration in plasma glucose levels in Japanese encephalitis patients

A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to produce hypoglycaemia during the convalescent stage in the plasma of patients with Japanese encephalitis virus (JEV) infection. The present study was undertaken to investigate the ability of T cells from fresh peripheral blood mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as the individual subpopulations, were cultured for 24 h and the culture supernatants (CS) were assayed for hypoglycaemic activity. The activity was observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients coincided with the gradual rise in circulating glucagon level, with no significant alterations in insulin, growth hormone and cortisol levels. The hTCHF was purified by ion exchange chromatography and the purified protein was observed as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of patients and T cell CS was present in 88% of convalescent serum samples. We conclude that during the convalescent stage of JEV infection, a unique factor, hTCHF, is secreted by activated CD8+ T cells from patients and that this is responsible for the development of hypoglycaemia.     

Morphine Stimulates Mesangial Cell TNF-α and Nitrite Production

Background: Intravenous opiate abusers are susceptible to develop heroin and HIV-associated nephropathies; however, the role of opiates in the development of these kidney lesions is not clear. Patients with opiate addiction are prone to recurrent infections. Methods: The effect of morphine was studied on the generation of TNF- with or without LPS (lipopolysaccharide) by cultured mouse mesangial cells. In addition, the effect of morphine was evaluated on mesangial cell nitrite production. To evaluate the role of opiate receptors, we studied the effect of naloxone and naltrexone on mesangial cell TNF- and nitrite production. To determine the role of TNF- on mesangial cell nitrite production, we examined the effect of anti-TNF- antibody on morphine-induced nitrite production. Assay of TNF- and nitrite production was carried by ELISA and Griess method respectively. Results: Morphine alone did not enhance the generation of TNF- by mesangial cells, however, an enhanced (P < 0.001) TNF- production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. Maximum release of TNF- was seen at a concentration of 10^–12 M of morphine. Opiate receptor antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite production. Anti-TNF- antibody attenuated morphine induced nitrite generation. Conclusion: We conclude that morphine stimulates the generation of TNF- by LPS-activated mesangial cells. This effect of morphine seems to be opiate receptor mediated and has a downstream effect in the form of mesangial cell nitrite generation. The present in vitro study provides the basis for a hypothesis that morphine may be playing a role in the development of heroin and HIV-associated nephropathies.     

Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model

We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated ¹²V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of ¹²V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.