Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear: NS may represent another manifestation of CMV disease.     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

Uveitis and immune responses in primates immunized with IRBP-derived synthetic peptides

Monkeys immunized with bovine IRBP-derived synthetic peptides R4 (sequence 1158-1180) or R14 (1169-1191) developed EAU which was detected by both clinical and histological examinations. The inflammation localized mainly in the choroid, with only minor changes being noticed in the adjacent retinal tissue. EAU developed in only one of the two monkeys immunized with each of the peptides and the animals with disease also showed higher levels of cellular immunity toward the immunizing peptide than did the monkeys with no disease. The cellular immune responses, measured by the lymphocyte proliferation assay, were specific toward the immunizing peptides, with no cross responsiveness to whole IRBP. This finding suggests that the two uveitogenic peptides were non-immunodominant in the tested monkeys. In contrast, peptide R14 is highly immunodominant in the Lewis rat. Also, the fine specificity of the monkey response to R14 differed from that of the Lewis rat. The possible genetic control of the monkey susceptibility to EAU induction by the peptides is discussed and the unique finding of an autoimmune disease induction by a non-immunodominant peptide is underscored.     

Early experience with a novel plaque excision system for the treatment of complex coronary lesions.

The use of directional coronary atherectomy (DCA) in current practice has been limited. The SilverHawk System is a newly developed plaque excision device that aims to overcome the drawbacks of prior DCA platforms. The device was evaluated in a porcine coronary model and in a series of patients. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) was performed and excised tissue fragments were weighed and examined histologically. In porcine cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases, pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and 15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show that the SilverHawk System may offer significant utility in treating a wide variety of complex coronary lesions.     

Alteration of Elastin, Collagen and their Cross-links in Abdominal Aortic Aneurysms

OBJECTIVES: although the mechanism of arterial dilation and aneurysm development has not been clarified, the degradation of elastin and collagen plays undoubtedly a critical role. We evaluated the elastin and collagen content through the detection of their cross-links in aneurysmal and non-aneurysmal abdominal aortic walls. MATERIALS AND METHODS: in 26 human abdominal aortic aneurysm specimens obtained during surgery and in 24 autopsy control samples of non-aneurysmal abdominal aorta the tissue content of elastin and collagen cross-links were measured by HPLC. Collagen was also detected by evaluating two characteristic amino acids, 4-hydroxyproline (4-hypro) with a colorimetric method and 5-hydroxylysine (5-hylys) by gas chromatography. RESULTS: significantly fewer elastin cross-links were found in aneurysm samples compared to controls (desmosines and isodesmosines: 90% reduction; p<0.01). The opposite was true for pyridinoline collagen cross-links (350% increase) and deoxypyridinolines (100% increase, p=0.01). Tissue content of 5-hylys, 4-hypro and total amino acids were reduced significantly by 50% in aneurysmal samples. CONCLUSIONS: beside confirming decreased elastin content in aneurysmal walls, these results show a concurrent increase of collagen cross-links. Since total collagen markers were decreased (decreased 4-hypro and 5-hylys) it is reasonable to suggest that in aneurysmal aortic walls old collagen accumulates cross-links while new collagen biosynthesis is somehow defective.     

Prevalence of hepatitis C infection in a hemodialysis unit.

To define the prevalence of NANB hepatitis, anti-HCV antibodies were determined in 51 patients on renal replacement therapy, in 7 transplanted patients and 17 staff members of the hemodialysis unit. Anti-HCV antibodies were evaluated using immunoenzymatic methods (Ortho HCV ELISA Test System, 1st and 2nd generation). Among hemodialysis patients, seroconversion was respectively documented in 17.6% (9/51) and 52.9% (27/51); none of the transplanted patients were positive with the 1st generation test, while 3/7 were positive with the 2nd. No statistically significant difference was found in the prevalence antibodies between transfused and nontransfused patients. ALT levels were statistically greater in patients with anti-HCV antibodies (X2 2nd generation = 8.83; p less than 0.01). Our results suggest: (1) that hemodialysis represents a risk factor; (2) the validity of substitute markers and (3) more sensitivity of the 2nd than 1st generation test.     

Problems in the design of anticancer agents

Theoretically, two predominant paths for obtaining more selective anticancer agents may be envisaged. These are: (a) to make compounds which distribute only or preferentially in cancer cells; (b) to make compounds that are able selectively to kill or to differentiate cancer cells. Although in the last two decades research into new anticancer drugs has not produced satisfactory results, there is solid ground on which novel strategies can be developed, mainly based on a much greater biological knowledge of human tumours. This article does not review all the possible approaches that may be followed, but simply discusses some ideas and problems mainly taken from the current research of our laboratory.     

Animal model for liver cell banking from non-heart beating donors after prolonged ischaemia time

BACKGROUND AND AIM: Although there is a growing interest on the use of non-heart beating donors to enlarge the liver donor pool, livers with prolonged warm ischaemia time are not currently considered for organ transplantation. We hypothesised that these organs may represent a source of hepatocytes for cell transplantation and/or use in bioartificial liver devices. Thus, we investigated if prolonged ischaemia could influence the recovery and viability of functional hepatocytes dissociated from rat livers. METHODS: Hepatocytes were isolated from the liver within 15 min after death (t=15 min) and after 4, 8 and 12h of ischaemia. Cells were either maintained in culture or cryopreserved. In all products, we evaluated cell recovery and viability, hepatocyte markers and cellular functions, including albumin and urea production. RESULTS: The number of cells per gram of tissue was similar at 15 min, 4 and 8h, while it was significantly decreased at 12h. About 0.2 x 10(6) viable cells expressing hepatocyte markers and producing albumin and urea were isolated up to 8h of ischaemia per gram of tissue. CONCLUSIONS: Recovery of viable and functional hepatocytes seems possible after prolonged ischaemia time. These data warrant the evaluation of hepatocyte isolation from human livers of non-heart beating donors.     

MRI, antibody-guided scintigraphy, and glucose metabolism in uveal melanoma.

To evaluate the usefulness of structural and biochemical imaging techniques for the diagnosis of uveal melanoma, 12 patients with choroidal melanoma were examined. Magnetic resonance imaging was used in 11 of 12 patients, as one had a metal prosthesis. All the subjects underwent single photon planar scintigraphy (SPPS) and single photon emission computed tomography (SPECT) using the 99mTc-labeled F(ab')2 of the anti-melanoma monoclonal antibody 225.28S ([99mTc]MoAb) and positron emission tomography (PET) using [18F]fluorodeoxyglucose ([18F]FDG). Magnetic resonance identified 6 of 11 melanotic lesions (definite melanomas) and 4 of 11 hypomelanotic lesions (probable melanomas), whereas in one case it was inconclusive. [99mTc]MoAb uptake was observed in 5 of 12 lesions using SPPS and 8 of 12 lesions using SPECT. [18F]FDG uptake was observed in 3 of 12 lesions by PET. These results demonstrate that both MR and radioimmunoscintigraphy are sensitive techniques for the diagnosis of choroidal melanomas and suggest that the detection of melanomas by MR, SPPS, and SPECT is largely dependent upon their size. The validity of these conclusions was verified in four subjects in whom the diagnosis was based on MR and/or SPECT findings only and confirmed by histology. The finding that only some of the uveal melanomas of larger size are visualized based on [18F]FDG uptake suggests that melanomas can have either high or low glucose consumption.