bluuebunny/crossref_metadata_2025 huggingface dataset:
The Serum Paraoxonase Activity in Patients with Chronic Renal Failure and Hyperlipidemia
Authors: Paragh György , Seres Ildikó , Balogh Zoltán , Varga Zsuzsa , Kárpáti István , Mátyus János , Újhelyi László , Kakuk György
Published: April 2003

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A1) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A1 levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A1 level decreases, we standardized the enzyme activity for HDL and Apo-A1 concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 ± 69.5) as compared with hyperlipidemic patients (137.64 ± 81.0) and controls (194.45 ± 94.45). The standardized values for Apo-A1 showed a similar tendency: paraoxonase/Apo-A1 ratio in uremic patients 89.64 ± 47.8, in hyperlipidemic patients 128.12 ± 69.83, and in controls 161.40 ± 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.
Simultaneous Improvement of Minimal-Change Nephrotic Syndrome and Anemia with Steroid Therapy
Authors: Yabana Machiko , Kihara Minoru , Toya Yoshiyuki , Tamura Kouichi , Matsumoto Katsumi , Takagi Nobuyoshi , Kamijo Seiko , Ishii Masao , Umemura Satoshi
Published: April 2003

A 56-year-old man presented with transient anemia in minimal-change nephrotic syndrome. Following nephrotic syndrome, anemia suddenly appeared without renal dysfunction. The anemia might be attributable to hemodilution because of significant correlations between the values of hemoglobin concentration and serum total protein or blood urea nitrogen during the clinical course. A low serum level and a low urinary excretion of erythropoietin were found, and when nephrotic syndrome ameliorated with steroid therapy, urinary erythropoietin excretion and anemia disappeared. This case indicated disappearance of the exponential increase of endogenous erythropoietin in acute anemia in nephrotic syndrome probably due to urinary losses and altered biosynthesis of erythropoietin. We report a case of the simultaneous improvement of both nephrotic syndrome and anemia with steroid therapy.
Detection of Cell Death of Cultured Mouse Mesangial Cells Induced by Oxidized Low-Density Lipoprotein
Authors: Tashiro Kyoichi , Makita Yuichiro , Shike Toshihide , Shirato Isao , Sato Taiji , Cynshi Osamu , Tomino Yasuhiko
Published: April 2003

The objectives of the present study using cultured mouse mesangial cells (MMC) were (1) to evaluate the type of cytotoxicity induced by oxidized (ox) LDL, i.e. apoptosis, necrosis and types of other cell death and (2) to investigate the pathway of cell death under incubation with antioxidants or scavenger receptor (SR) antagonists. LDH release and a morphological examination were used in this study. Trypan blue staining of MMC was performed to detect dead cells in culture. Cytotoxicity of ox-LDL in MMC was found to be dose- and time-dependent. In the morphological study of electron microscopy, three different types of cell death in ox-LDL-treated MMC were identified. In the morphological study with semithin sections, these three types of dead cells were identified at different dosages of ox-LDL. Type 1 or type 2 dead cells were observed in low dose ox-LDL or in middle-dose ox-LDL-treated MMC, respectively. Type 3 dead cells were marked in high dose ox-LDL-treated MMC. It appears that the cells were apoptotic (type 1), necrotic (type 3) and other types (type 2). The cytotoxicity of ox-LDL was not mediated by cellular internalization of ox-LDL via SRs. On the other hand, the cytotoxicity of ox-LDL was inhibited by antioxidants such as α-tocopherol, probucol, N-acetyl-cysteine or glutathione ethyl ester. It is indicated that the pathways of ox-LDL induced cell death were distinct from the pathway via SRs.
Clinicopathologic Correlations in Lupus nephritis in Lima, Peru
Authors: Hurtado Abdias , Asato Carmen , Escudero Elizabeth , Stromquist Chris S. , Urcia Jaime , Hurtado Maria Elena , de la Cruz Sonia , Wener Mark H. , Zavala Rodolfo , Johnson Richard J.
Published: April 2003

Background: We assessed whether immunohistologic markers for glomerular or tubulointerstitial injury might provide better correlations with ongoing renal function and disease activity as compared with the WHO classification or the NIH activity and chronicity indices in lupus nephritis. Methods: Thirty-three patients with clinically defined systemic lupus underwent renal biopsy over a 1-year period at Hospital Loayza in Lima, Peru. Biopsy specimens were evaluated for macrophages, proliferating cells, α-actin expression, and type IV collagen deposition in both glomeruli and the tubulointerstitium and the results compared with the current WHO and NIH classifications in relation to the clinical presentation. Results: Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria and hematuria, and worse renal function. An elevated NIH activity index correlated with microhematuria, proteinuria, and impaired renal function, whereas an elevated chronicity index correlated with renal function, hypertension, and microhematuria, but not with proteinuria. The presence of glomerular macrophages correlated with both glomerular α-actin expression and type IV collagen deposition, but did not correlate with renal function or proteinuria. In contrast, interstitial macrophages correlated not only with interstitial collagen deposition and myofibroblast accumulation, but also correlated with both renal function and the presence of nephrotic syndrome. Conclusions: Both the WHO classification and the NIH activity/chronicity indices correlate with clinical manifestations of lupus nephritis. While glomerular macrophage accumulation correlates with mesangial cell activation (α-actin expression) and collagen deposition, and interstitial macrophage accumulation correlates with interstitial fibroblast activation and collagen deposition, only interstitial macrophages correlate with renal function. Of particular interest will be future studies to determine whether these markers correlate with the prognosis.
Effect of Short-Term rHuEPO Treatment on Insulin Resistance in Haemodialysis Patients
Authors: Spaia Sophia , Pangalos Manolis , Askepidis Nikolaos , Pazarloglou Michalis , Mavropoulou Eleni , Theodoridis Stelios , Dimitrakopoulos Kostas , Milionis Antonios , Vayonas George
Published: April 2003

Background/Aim: Decreased sensitivity to the hypoglycaemic action of insulin is an almost universal phenomenon in uraemic patients, and it is attributed either to uraemic toxins or to anaemia or even to secondary hyperparathyroidism. Considering the conflicting data of few existing studies, we examined the influence of erythropoietin (EPO) treatment on insulin resistance and tested the probable correlation of this influence with sympathetic nervous system (SNS) activity. Methods: We studied 8 non-obese, non-diabetic, stable dialysis patients using the euglycaemic insulin clamp technique before administration of EPO (phase A), 10 days after (phase B), and after the correction of the haematocrit level, at least 8 weeks later (phase C). We estimated the indices (glucose infusion rate, mg/kg/min), M/G (glucose clearance), and M/I (tissue sensitivity to insulin), and we measured haematocrit, haemoglobin, triglyceride, ferritin, EPO, and fasting insulin levels in each phase. During each phase, we tested the SNS activity using the response of blood pressure to persistent handgrip and the response of blood pressure to the standing position. Results: Our patients appeared to have an increased insulin resistance in phase A (MA = 6.24 ± 1.01) which was significantly improved 10 days after the beginning of EPO treatment and before the rise of haematocrit (MB = 7.71 ± 1.54, p < 0.05). There was no further improvement in phase C. Indices M/G and M/I behaved similarly. The serum triglyceride levels decreased in response to the increased insulin sensitivity. The patients studied did not demonstrate fasting hyperinsulinaemia, while the SNS activity was abnormal and remained unchanged throughout the study period in spite of some individual improvement. Conclusions: Our study proves the beneficial effect of EPO treatment on insulin resistance in dialysis patients which could be attributed to the EPO itself and not to the correction of anaemia and is accompanied by improvement in triglyceride levels. Amelioration of insulin resistance did not influence the SNS activity, making the association between EPO treatment and SNS-derived changes in blood pressure quite improbable.
Responses of the Skin Microcirculation to Acetylcholine in Patients with Essential Hypertension and in Normotensive Patients with Chronic Renal Failure
Authors: Cupisti Adamasco , Rossi Marco , Placidi Silvia , Fabbri Alessandra , Morelli Ester , Vagheggini Guido , Meola Mario , Barsotti Giuliano
Published: April 2003

Aims: To assess the endothelial function of the skin microcirculation in chronic renal failure (CRF) independent of hypertension, we investigated the changes of the cutaneous blood flow induced by iontophoretic delivery of acetylcholine (ACh) and of sodium nitroprusside (SNP) in CRF patients free from arterial hypertension and in patients with essential hypertension. Methods: The study included 20 patients affected by CRF (mean creatinine clearance 12 ± 2 ml/min) without arterial hypertension (mean blood pressure 96 ± 1 mm Hg), 15 patients affected by essential hypertension (mean blood pressure 124 ± 1 mm Hg), and 20 normal controls. The changes of skin blood flow following iontophoretic delivery of ACh and of SNP were measured by laser Doppler flowmetry. Results: Following maximal ACh or SNP delivery, the change of blood flow from the baseline was similar both in normals (683 ± 92 vs. 684 ± 87%) and in CRF patients (778 ± 108 vs. 803 ± 124%), whereas in the hypertensives the response to ACh was lower than to SNP (434 ± 48 vs. 702 ± 98%, p < 0.01). Since the third ACh delivery dose, the skin blood flow increments were significantly lower in the hypertensive than in the CRF or in the normal control groups, whereas no difference was observed between uremics and controls. Conclusions: The endothelium-dependent hyperemia following ACh iontophoretic delivery is impaired in the skin microcirculation of essential hypertensive patients, but this is not the case in CRF patients with no history of arterial hypertension. This suggests that CRF per se, independent of arterial hypertension, is not associated with endothelial dysfunction of skin microcirculation.
Differences between Blood Flow as Indicated by the Hemodialysis Blood Roller Pump and Blood Flow Measured by an Ultrasonic Sensor
Authors: Teruel J.L. , Fernández Lucas M. , Marcén R. , Rodríguez J.R. , López Sánchez J. , Rivera M. , Liaño F. , Ortuño J.
Published: April 2003

Background/Aim: The ultrasonic transit time is currently the best method for measuring the blood flow rate in the extracorporeal hemodialysis circuit. The purpose of this study was to analyze the differences between blood flow as indicated by the hemodialysis blood roller pump (prescribed blood flow) and by an ultrasonic flowmeter (delivered blood flow). Methods: The ultrasonic blood flow was measured in 20 patients on chronic hemodialysis who were dialyzed through an arteriovenous fistula. During each dialysis session the ultrasonic blood flow was measured at three different blood roller pump flow rates (300, 350, and 400 ml/min). In order to analyze the influence of inflow and outflow pressures on blood flow, this study was conducted during nine consecutive dialysis sessions during which needles of different sizes were used. Results: The ultrasonic flow was always lower than indicated by the blood roller pump: 265 ± 12, 304 ± 15, and 341 ± 19 ml/min for blood roller pump flow rates of 300, 350, and 400 ml/min, respectively (variability: –11.6, –13.1, and –14.8%, respectively). An univariate regression analysis showed that the reduction in flow recorded ultrasonically correlated with both venous blood line pressure (r = –0.2679, p < 0.001) and negative arterial blood line pressure (r = 0.6773, p < 0.001). By multivariate analysis, only the arterial blood line pressure has a predictive value. When all measurements were grouped by arterial blood line pressure ranges, the variability between ultrasonic blood flow and blood roller pump flow was found to be similar in those groups with the same arterial blood line pressure, regardless of the blood roller pump flow rate. Conclusions: The blood flow indicated by the dialysis blood roller pump is always greater than the delivered blood flow, and this difference is in turn conditioned by the negative pressure induced by the blood roller pump in the arterial blood line.
Urinary Excretion of Type IV Collagen as a Specific Indicator of the Progression of Diabetic Nephropathy
Authors: Watanabe Hidetsuna , Sanada Hironobu , Shigetomi Shuichi , Katoh Tetsuo , Watanabe Tsuyoshi
Published: April 2003

Aims and Methods: This study was carried out to clarify whether the urinary excretion of type IV collagen (u-IV collagen) detected by specific radioimmunoassay, can be used as an indicator for the progression of diabetic nephropathy. Results: u-IV collagen was higher in diabetic subjects with microalbuminuria and overt proteinuria than those with normoalbuminuria, IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, or control normal subjects. u-IV collagen was positively correlated with serum and urinary β2-microglobulin and negatively with creatinine clearance only in diabetic patients, but not in patients with other glomerular diseases. The serum type IV collagen was not different between all the groups, and not correlated with its urinary excretion. In the advanced diabetic nephropathy, immunoreactive type IV collagen was detected in glomerular basement membrane (GBM), tubular basement membrane and Bowman’s capsule much more than that in the normal kidney. Conclusion: These findings indicated increased production and degeneration of type IV collagen in diabetic nephropathy. It is suggested that augmented turnover of type IV collagen in GBM and tubular basement membrane results in increased concentrations of free u-IV collagen. Therefore, measurement of u-IV collagen may be a useful, specific indicator of the progression of diabetic nephropathy.
Influence of Long-Term Diabetes on Renal Glycogen Metabolism in the Rat
Authors: Nannipieri Monica , Lanfranchi Alberto , Santerini Daniele , Catalano Carlo , van de Werve Gérald , Ferrannini Ele
Published: April 2003

Background/Aims: The effects of acute insulin deficiency on the kidney have been investigated in animal models of experimental diabetes; however, the impact of long-term diabetes has not been determined. Methods: We measured renal glycogen contents in streptozotocin (STZ)-diabetic rats 3 weeks (n = 12) or 9 months (n = 12) after the induction of diabetes, and in 2 groups of control rats of similar age (n = 16 and n = 12, respectively), in the fed state and after a 24-hour fast. Results: Diabetic rats had high glucose levels, low insulin but normal glucagon concentrations in portal blood. In the fasting state, kidney glycogen content was very low in both young control and young diabetic rats (54 ± 15 and 189 ± 26 µg/g, respectively, mean ± SD); in contrast, glycogen levels were markedly elevated in rats with long-standing diabetes as compared to old nondiabetic animals (2,628 ± 1,023 ± and 1,968 ± 989 µg/g of diabetic rat, fasting and fed, respectively, p < 0.001 vs. 0 ± 0 and 4 ± 6 µg/g of control rats). On electron microscopy, large glycogen clusters were localized to the renal tubules. Kidney phosphorylase activity was higher, and synthase activity lower in diabetic than control rats (p < 0.05 for both), whereas kidney glycogen was strongly related to plasma glucose levels, suggesting that the enzyme changes were secondary to glycogen accumulation itself. Renal hexosephosphates and fructose-2,6-bisphosphate contents were both increased in long-term diabetic rats (p < 0.05), implying enhanced fluxes through both glycolysis and gluconeogenesis. Conclusion: In chronic, untreated diabetes glycogen accumulates in the renal tubules; prolonged hyperglycemia is the sole driving force for this phenomenon.
Nucleotide Sequence and Expression of Rat β-Defensin-1: Its Significance in Diabetic Rodent Models
Authors: Hiratsuka Takeaki , Nakazato Masamitsu , Date Yukari , Mukae Hiroshi , Matsukura Shigeru
Published: April 2003

β-Defensins are epithelium-derived antimicrobial peptides that function in the host’s innate defense. We identified the first member of the rat β-defensin family, β-defensin-1 (BD-1), in the kidney and determined its nucleotide sequence. It was predicted to be a 37-amino-acid peptide. Rat BD-1 mRNA was expressed most abundantly in the kidney, next in skin, tongue, esophagus, and uterus, followed (at low levels) by brain, trachea, stomach, urinary bladder, and ovary. BD-1 gene expression in rat kidney was not increased by lipopolysaccharide administration. BD-1 gene expressions in the kidneys of diabetic rodent models, cholecystokinin-insensitive Otsuka Long-Evans Tokushima Fatty rats, leptin-insensitive obese (fa/fa) Wistar rats, and db/db mice, were significantly lower than those of their lean littermates. BD-1 reduction may be in part responsible for the high incidence of urinary tract infections in diabetes mellitus.
Long-Term Results of Donor-Specific Blood Transfusion with Cyclosporine in Living Related Kidney Transplantation
Authors: Otsuka M. , Yuzawa K. , Takada Y. , Taniguchi H. , Todoroki K. , Fukao K. , Koyama A. , Akaza H.
Published: April 2003

Donor-specific blood transfusion (DST) was introduced to achieve better graft survival. However, its benefits are controversial considering the immunosuppression of cyclosporine (CYA) or tacrolimus (Tac), and its long-term effects have not been well discussed. Of the 40 patients who received DST with CYA, 3 (7.5%) became cross-match positive. Of the 37 patients with negative cross-match, 34 patients received a one-haplotype-matched kidney and were compared to patients with one-haplotype-matched kidney transplant without preoperative DST (n = 13). Acute rejection within 3 months after transplant was 29.4% in the DST group, and 15.4% in the non-DST group. All rejection episodes were steroid resistant in the non-DST group. If the graft survival rates were calculated excluding non-immunological graft loss, graft survival rate was 91.0 and 72.8% at 5 and 10 years in the DST group, and 83.3% at 5 and 10 years in the non-DST group, respectively. The two graft survival lines converged 7 years and 7 months after transplantation. No beneficial effect of DST was statistically evident under CYA immunosuppression. In terms of the severity of acute rejection or the onset of chronic rejection, DST induced a small benefit, however, which seemed to disappear within 8 years after transplantation.
Are Uraemic Children Immunologically Compromised?
Authors: Ensari Cüneyt , Ekim Mesiha , Ikinciogullari Aydan , Tümer Necmiye , Ensari Arzu
Published: April 2003

Background: Various immunological abnormalities leading to impaired immune status have been described in uraemic adults; however, few data are available for uraemic children. Methods: In this study, peripheral blood total lymphocyte count and lymphocyte subsets (CD3+, CD4+, CD8+, CD16+, CD20+) were evaluated, skin tests with PPD and Candida antigens were performed, and serum immunoglobulin (IgG, IgA, IgM) and complement (C3, C4) levels were measured in 30 children with end-stage renal failure (10 before dialysis, 10 on continuous ambulatory peritoneal dialysis, and 10 on haemodialysis) and the results compared with those of 15 healthy controls. Results: The data showed significant lymphopenia in predialysis and haemodialysis groups. No significant change was observed in the CD4+/CD8+ ratio or in the percentages of lymphocyte subsets in either group studied, while the absolute values of some lymphocyte subsets were significantly lower in all groups as compared with controls. In skin test evaluation, only the patients in the predialysis group showed a significantly decreased response to Candida antigen. The serum immunoglobulin levels were significantly decreased in the continuous ambulatory peritoneal dialysis group as compared with the control group. Conclusion: Our results, together with those of other paediatric studies, reported in the literature, suggest that uraemic children are not immunocompromised, though the effects of uraemia may cause some variation in their immune status.
Retinopathy, Hematuria, and Diabetic Nephropathy
Authors: Izzedine Hassane , Fongoro Sahare , Pajot Olivier , Beaufils Hélène , Deray Gilbert
Published: April 2003

We have retrospectively analyzed the incidence of diabetic nephropathy in 21 diabetic patients who underwent renal biopsy between 1985 and 1995 for microscopic hematuria and/or proteinuria >2.5 g/day without retinopathy. Diabetic nephropathy was observed in 13 of 21 patients (62%). 50% of our patients with diabetic nephropathy had hematuria, the incidence being higher in type I as compared with type II diabetic patients (30 vs. 20%). Diabetic nephropathy without retinopathy but with hematuria was noted in 5 of 13 patients, and diabetic nephropathy without retinopathy and hematuria was also noted in 5 of 13 patients. We suggest from our retrospective analysis that renal-retinal diabetic syndrome really exists.
Cerebral Imaging Changes in Patients with Chronic Renal Failure Treated Conservatively or in Hemodialysis
Authors: Savazzi Giorgio M. , Cusmano Ferdinando , Musini Sabrina
Published: April 2003

Background: Nonuremic patients with apparently normal memory and behavior, studied by means of cerebral computed tomography and found to have cerebral atrophy (CA), evidenced functional intellectual deficits when they underwent psychometric testing. The finding of CA has been repeatedly reported in limited case groups of uremic patients who also demonstrated functional intellectual deficits on the basis of the same tests. This retrospective study considered all diagnostic cerebral computed tomography scans done in our department between 1981 and 1998. Fifty-five uremic patients in conservative treatment (CT) and 111 patients in hemodialysis treatment (HT) were selected on the basis of the following two criteria: primary nephropathy as the cause of uremia and an age ≤55 years to exclude involutive brain changes occurring with age. Aims: The aims of the study were to determine the percent of uremic patients with CA, the characteristics of their CA (cortical or subcortical), and eventual associated morphological lesions. Results: CA was detected in 50.9% (cortical atrophy in 47.3% and subcortical atrophy in 3.6%) of the uremic patients in CT and in 77.5% of those in HT (cortical atrophy in 65.7% and subcortical atrophy in 7.7%). The average degree of CA was 0.872 in the patients in CT and 1.765 in the patients in HT. Thirty-four of the patients in the CT group and 46 in the HT group were hypertensive: these patients had a more severe degree of CA than the nonhypertensive subjects. In the CT group, the degree of CA in the hypertensive patients was 1.205 versus 0.428 for the nonhypertensive subjects. In the HT group, the degree of CA was 2.087 for the hypertensive patients versus 1.538 for the nonhypertensive patients. Of the overall population, 7.8% had ischemic lesions, 9.6% had endocranial calcifications, and 5.4% evidenced periventricular white matter hyperintensities. Conclusions: The high percent of CA found in young uremic patients increased in subjects in HT and, even more so in hypertensive patients. Vascular calcifications, focal ischemia and leukoaraiosis, well-known expressions of a chronic state of cerebrovascular insufficiency, were also found in HT patients; hypertension alone is a recognized accelerator of vascular damage. Thus, early and severe atherosclerosis and related hypoperfusion can be considered as the paramount causes of parenchymal cerebral damage in uremia.
Metronidazole-Induced Encephalopathy in a Uremic Patient: A Case Report
Authors: Arık Nurol , Cengiz Nilgün , Bilge Ahmet
Published: April 2003

A variety of neurologic disorders may develop in patients with chronic renal failure. Drug toxicity must be thought of in the differential diagnosis of these disorders. We report a case with renal failure developing serious neurotoxicity after metronidazole use.
Significantly Rapid Relief from Steroid-Resistant Nephrotic Syndrome by LDL Apheresis Compared with Steroid Monotherapy
Authors: Muso Eri , Mune Masatoshi , Fujii Yasuhiro , Imai Enyu , Ueda Naohiko , Hatta Kazuhiro , Imada Akio , Takemura Tsukasa , Miki Shozo , Kuwahara Takashi , Takamitsu Yoshihiro , Tsubakihara Yoshiharu
Published: April 2003

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.
Human Perinatal Asphyxia: Correlation of Neonatal Cytokines with MRI and Outcome
Authors: Foster-Barber Audrey , Dickens Benjamin , Ferriero Donna M.
Published: April 2003

Clinical studies of the preterm neonate and animal models of asphyxial brain injury both support a role for proinflammatory cytokines in central nervous system (CNS) injury. There are fewer studies of perinatal CNS injury in the full-term neonate. We have performed a prospective cohort study of full-term infants with perinatal asphyxia. Using archived neonatal blood samples, we have analyzed the serum levels of several proinflammatory cytokines. Preliminary results demonstrate an increase in IL-1, IL-6, and TNF-α in those children who are deceased at 1 year or who have a diagnosis of cerebral palsy versus those with normal neuromotor outcome. Further analysis will include correlations of cytokine levels with injury on MRI spectroscopy, with neonatal clinical markers of encephalopathy, and with later neurodevelopmental outcome.
Hemodialysis with Two Sequential Hemodialyzers
Authors: Splendiani Giorgio , Zazzaro Dario , Tullio Tiziana , Colombo Roberto , Violante Anneo , Beciani Marta
Published: April 2003

Background/Aims: The principal aims of the new hemodialysis methods are: a short-time dialysis session, the increase of solute removal, the patient’s well-being and, when possible, the reduction of global costs. Other researchers have experimented the simultaneous use of two hemodialyzers in hemodialysis. We tested a new technique which involves the use of two Cuprophan hemodialyzers in sequence (double filter system: DFS), each one connected separately to fresh dialysate. Methods: We treated 15 large patients with DFS and compared the results with conventional hemodialysis (CHD). Results: Our results showed a significant difference between CHD and DFS in the depuration values. After the first hemodialyzer, modification of pH and electrolytes occurred in the plasma composition. In the second hemodialyzer, urea depuration occured without further significant changes in hydroelectrolytic and acid-basic plasma patterns. The Kt/V increased from 1.10 to 1.29 (18%). Conclusion: Our technique is conceived for the following goal: to increase the diffusion of solution without increasing costs and side effects.
Transmission of G-Protein β3 Subunit C825T Alleles to Offspring Affected with End-Stage Renal Disease
Authors: Gumprecht Janusz , Zychma Marcin J. , Grzeszczak Wladyslaw , Zukowska-Szczechowska Ewa
Published: April 2003

Background: Results of epidemiological studies have suggested that a hereditary predisposition to the development of chronic renal failure exists, and that such predisposition might be independent from underlying etiology of kidney disease. On the other hand, high blood pressure contributes substantially to a faster rate of progression of renal damage, regardless of underlying etiology of kidney disease. In this study we tested whether GNB3 C825T polymorphism, previously reported to be associated with hypertension, contributes to predisposition to end-stage renal disease (ESRD). Methods:GNB3 polymorphism was genotyped in 247 family trios: offspring affected with ESRD and both parents, and transmission/disequilibrium test was used to establish the allele-phenotype association. Among the examined offspring, 47 patients had ESRD in the course of type 1 diabetes and diabetic nephropathy, 120 had primary glomerulonephritis and 80 had interstitial nephritis. We observed no significant differences between the GNB3 C and T allele transmission from heterozygous parents to affected offspring. Results: In the overall group of examined patients, the C:T allele transmission (%) was 48:52, while in patients with diabetic nephropathy, chronic glomerulonephritis and chronic interstitial nephritis the transmission was (%) 50:50, 48:52 and 48:52, respectively. Conclusion: The results of our study suggest that GNB3 C825T polymorphism does not contribute substantially to the increased risk of the development of ESRD.
Erythropoietin Requirements Increase following Hospitalization in End-Stage Renal Disease Patients
Authors: Yaqub Muhammad S. , Leiser Jeffery , Molitoris Bruce A.
Published: April 2003

The effect of hospitalization on an ESRD patient’s hemoglobin (Hgb) level and erythropoietin (Epo) requirement has not been investigated. We postulated patients with end stage renal disease required an increased Epo dose to maintain stable Hgb during hospitalization and for a period following discharge. To evaluate this hypothesis, we conducted a retrospective chart review on 65 hemodialysis patients. All hemodialysis patients admitted for more than 2 days who did not have more than the index hospitalizations for 2 months prior to and following discharge were included. Multiple parameters including Hgb, Epo dose, intravenous iron dose, serum iron, TIBC, and ferritin during the 2 months before and the two months after hospitalization, Hgb at admission and discharge, Hgb trough, surgery, blood transfusions and co-morbid factors were evaluated. Statistical significance was evaluated using ANOVA or rank-sum testing, as appropriate. In 65 hemodialysis patients (24 M/41 F, age 58 ± 2.2 years, mean ± SEM), Hgb levels following discharge and for 2 subsequent months were significantly lower than 2 months prior to admission (11.4 ± 0.25 vs. 10.7 ± 0.22 g/dl, p < 0.01). This occurred in spite of an increase in Epo dose (128 ± 14 vs. 185 ± 21 U/kg/week, p < 0.0001) over this 2-month period. There was no difference in the iron saturation before and after hospitalization (22 vs. 23%,p > 0.05). There were also no apparent effects of comorbid factors, including surgery, or discharge diagnosis on the changes in Hgb or Epo requirements. However, patients who required a blood transfusion during the hospitalization had lower Hgb levels and higher Epo doses both prior to and after hospitalization, as well as lower Hgb trough levels. In addition, females had lower Hgb levels than males both prior to and after hospitalization, and were receiving a higher Epo dose 191 ± 18 vs. 129 ± 20 U/kg/week at 1 month and 215 ± 18 U/kg/week vs. 134 ± 22, p < 0.005 at 2 months after hospitalization. Conclusion: This study points out that hemodialysis patients experience a significant and prolonged decrease in Hgb levels after hospitalization, even despite a moderate increase in Epo dosing.
Struvite Stones
Authors: Rodman JohnS.
Published: April 2003

Struvite stones constitute only about 2–3% of the stones reaching the laboratory for analysis, but the clinical problems they create including sepsis and even renal demise are greater than with any other stone type. This article reviews the evidence that bacterial urease, usually from a Proteus species, is responsible for the chemical changes in urine which result in struvite formation. Available urease inhibitors and other forms of medical management of patients with these stones are discussed. A patient with struvite stones should be assumed to have a progressive disease which cannot be ignored. Even after seemingly successful elimination of stones with lithotripsy and/or percutaneous nephrolithotomy, careful medical follow-up is critical. The medical profession is probably underutilizing postprocedure hemiacidrin irrigation because of shortsighted financial considerations. Primary-care physicians need to be educated in the importance of aggressive management of Proteus and other urea-splitting infections.
Remarkably Reduced Transplant-Related Complications by Dibromomannitol Non-Myeloablative Conditioning before Allogeneic Bone Marrow Transplantation in Chronic Myeloid Leukemia
Authors: Barta Anikó , Dénes Róbert , Masszi Tamás , Reményi Péter , Bátai Árpád , Torbágyi Éva , Sipos Andrea , Lengyel Lilla , Jakab Katalin , Gyódi Éva , Réti Marienn , Földi János , Páldi-Haris Piroska , Avalos Manuel , Pálóczi Katalin , Fekete Sándorné , Török Judit , Hoffer Izabella , Jakab Judit , Váradi Gábor , Kelemen Endre , Petrányi Győző
Published: April 2003

A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II–IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III–IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7–29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients.
Hematologic and Immunophenotypic Characterization of Human Umbilical Cord Blood
Authors: Pranke Patricia , Failace Renato R. , Allebrandt Waldir F. , Steibel Gustavo , Schmidt Francisco , Nardi Nance Beyer
Published: April 2003

In this work, cord blood cells from 30 healthy term newborns were analyzed for complete blood counts with an automated cytometer and, in part of the sample, for surface molecules in cord blood monocytes, lymphocytes and CD34+ cells by two-color flow cytometry. Hematological parameters were as follows: WBC = 12.85 (5.24–15.10) ×109/l; platelets = 304.33 (156.00–469.00) × 109/l; Hb = 14.45 (11.90–17.82) g/dl; RBC = 3.99 (3.14–5.12) × 1012/l; MCV 107.25 (99.60–115.00) fl; reticulocytes = 157.80 (101.00–124.00) × 109/l or 3.99 (2.45–6.01)%; erythroblasts = 0.88 (0.15–2.58) per 100 WBC or 6.63 (2.86–16.80) × 109/l. The mononuclear population, as evaluated by flow cytometry, was composed of 22.9 ± 7.2% monocytes and 77.05 ± 7.24% lymphocytes, among which 46.59 ± 15.62% were T lymphocytes (43.94 ± 16.94% CD3+/CD4+ and 13.45 ± 7.46% CD3+/CD8+). CD34+ cells were on average 0.54 ± 0.24% of the mononuclear fraction. CD11c, CD49e and HLA-DR were found mainly on monocytes, and CD31 and CD62L occurred in similar levels on monocytes and lymphocytes. CD117+ cells were less than 5% of these populations. Among CD34+ cells, CD31 and HLA-DR were the molecules with higher frequencies (79.7 ± 19.9 and 65.7 ± 23.0%, respectively), followed by CD62L (41.8 ± 31.9%) and CD117 (20.1 ± 15.8%). The presence of CD11c and CD49e on CD34+ cells was low (below 10%). The results stress the phenotypic heterogeneity of cord blood CD34+ cells, and the different behavior of the cells when manipulated in vitro in different degrees of isolation.
Epidemiology of Thrombosis in Cancer
Authors: Rickles Frederick R. , Levine Mark N.
Published: April 2003

We have utilized epidemiological data to address three questions in patients with cancer and venous thromboembolism (VTE): (1) What is the risk for occult cancer in patients with idiopathic versus secondary VTE? (2) What is the risk for thrombosis in patients with cancer (vs. noncancer patients)? (3) What is the risk of recurrent VTE in cancer patients with an initial episode of VTE compared to noncancer patients? The risk for a new cancer diagnosis within 6–12 months of the diagnosis of idiopathic VTE (including pulmonary embolism) is well supported by retrospective analyses of large numbers of unselected patients, population-based retrospective cohort analyses from large registries and prospective studies. The odds ratios for these studies are in the range of 4- to 7-fold increased risk. In surgical patients with known cancer the odds ratio for an episode of postoperative VTE is approximately 2, when compared to a control group of noncancer patients subjected to the same procedures. A similar odds ratio of approximately 2 exists for the relative risk for recurrence of VTE in the first 3 months after an initial episode in cancer patients treated with heparin and warfarin (Coumadin®) compared to noncancer patients. Therefore, patients with idiopathic VTE are at increased risk for occult cancer and cancer patients are at increased risk for VTE. Appropriate studies are underway to determine the best strategies for anticoagulant management of these patients.
The Role of Vascular Endothelial Growth Factor in Angiogenesis
Authors: Ferrara Napoleone , Gerber Hans-Peter
Published: April 2003

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenic inducer as well as a mediator of vascular permeability. The biological effects of VEGF are mediated by two tyrosine kinase receptors, Flt-1 (VEGFr-1) and KDR (VEGFR-2). VEGF is essential for developmental angiogenesis and is also required for female reproductive functions and endochondral bone formation. Substantial evidence also implicates VEGF in tumors and intraocular neovascular syndromes. Currently, several clinical trials are ongoing to test the hypothesis that inhibition of VEGF activity may be beneficial for these conditions.
Advances in the Treatment of Relapsed Acute Promyelocytic Leukemia
Authors: Douer Dan
Published: April 2003

The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-α (PML-RARα), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Multiple studies have established that combination of ATRA and chemotherapy in newly diagnosed patients has increased the cure rate to 70% from 35% in patients treated with chemotherapy alone. However, still about 30% of the patients relapse and are often resistant to ATRA retreatment. Consequently, a number of novel agents that include several differentiation agents and monoclonal antibodies have been studied to provide improved outcomes for patients with APL who have relapsed. In particular, arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. The unique mechanisms of action by which arsenic trioxide exerts its effects are complementary to those of ATRA, potentially allowing for combination therapies with additive or even synergistic results. Within this context autologous or allogeneic bone marrow transplantations are also considered in second or subsequent relapse, especially after arsenic trioxide-induced complete remission in relapsing patients. Furthermore, molecular monitoring for the PML-RARα fusion protein permits prompt intervention for early molecular relapse of APL before clinical relapse, ultimately improving chances of prolonged remission.
An Overview of Translocation-Related Oncogenesis in the Chronic Myeloid Leukaemias
Authors: Bain Barbara J.
Published: April 2003

The demonstration of the BCR-ABL fusion gene in patients with chronic granulocytic leukaemia and t(9;22)(q34;q11) represents the first recognition, in a human neoplasm, of a translocation leading to formation of an oncogenic fusion gene. Since this initial observation, this leukaemogenic mechanism has been increasingly recognized in chronic myeloid leukaemias. The fusion gene has often incorporated part of a gene encoding a receptor or cytoplasmic tyrosine kinase, particularly ABL, PDGFRB and FGFR1. This contrasts with the frequent involvement of genes encoding transcription factors or other nuclear proteins in acute myeloid leukaemia. Nevertheless, genes encoding tyrosine kinases have also been implicated in some cases of acute leukaemia. With the exception of the BCR-ABL fusion gene in chronic granulocytic leukaemia, all these fusion genes are uncommon or rare among cases of chronic myeloid leukaemia. The molecular mechanisms underlying the great majority of cases of Philadelphia-negative chronic myeloid leukaemia remain to be discovered.
The 8p11 Myeloproliferative Syndrome: A Distinct Clinical Entity Caused by Constitutive Activation of FGFR1
Authors: Macdonald Donald , Reiter Andreas , Cross Nicholas C.P.
Published: April 2003

Several recurrent translocations that involve chromosome band 8p11 have been described in myeloid malignancies. These translocations target two distinct genes: (1) FGFR1, a receptor tyrosine kinase for fibroblast growth factors, and (2) MOZ, a putative histone acetyltransferase whose precise function remains to be defined. Disruption of FGFR1 is associated with a disease entity known as the 8p11 myeloproliferative syndrome (EMS)/stem cell leukemia-lymphoma syndrome, a chronic myeloproliferative disorder that frequently presents with eosinophilia and associated T-cell lymphoblastic lymphoma. The disease is aggressive and rapidly transforms to acute leukaemia, usually of myeloid phenotype. Currently, only allogeneic stem cell transplantation appears to be effective in eradicating or suppressing the malignant clone. To date, four gene fusions associated with distinct translocations have been described in EMS: the t(8;13)(p11;q12), t(8;9)(p11;q33), t(6;8)(q27;p11) and t(8;22)(p11q22) fuse ZNF198, CEP110, FOP and BCR, respectively, to FGFR1. The resulting fusion proteins have constitutive tyrosine kinase activity and activate multiple signal transduction pathways. These pathways and the fusion proteins are attractive targets for targeted signal transduction therapy.
Prevalence of Nephropathy in Black Patients with Type 2 Diabetes mellitus
Authors: Gitter James , Langefeld Carl D. , Rich Stephen S. , Pedley Carolyn F. , Bowden Donald W. , Freedman Barry I.
Published: April 2003

The prevalence of nephropathy in black patients with type 2 diabetes mellitus is poorly defined. We performed a cross-sectional analysis of 98 unrelated and unselected black type 2 diabetic patients treated in indigent care internal medicine clinics to determine the prevalence of proteinuria and nephropathy. Serum creatinine, blood urea nitrogen, urine albumin and urine creatinine concentrations were measured. A Spearman’s rank correlation was computed to test for a relationship between diabetes duration and continuous outcomes. For binary outcomes, an odds ratio and 95% confidence interval were computed for a change of 10 years diabetes duration based on logistic regression. Cases were 61% female, and had mean (± SD) age 59.9 ± 12.5 years, diabetes duration 12.6 ± 9.4 years, body mass index 32.4 ± 9.3 kg/m2, hemoglobin A1C (HbA1C) 9.2 ± 2.3%, and serum creatinine concentration 1.60 ± 1.1 mg/dl. For continuous variables, diabetes duration was positively associated with albuminuria (r = 0.31; p = 0.0017), serum creatinine (r = 0.36; p = 0.0003) and blood urea nitrogen concentration (r = 0.36; p = 0.0003). For binary variables, cases with longer diabetes duration were at increased risk for urinary albumin:creatinine >300 µg/mg (p = 0.006), elevated serum creatinine concentration (≧1.4 mg/dl in women or ≧1.6 mg/dl in men; p = 0.045), elevated blood urea nitrogen concentration (≧20 mg/dl; p = 0.026), and clinical cerebrovascular disease (p = 0.028). HbA1C, body mass index, and blood pressure did not correlate with diabetes duration in this population. Among the cases, 33.7% had elevated serum creatinine concentration and 71.5% had abnormal levels of albuminuria (27.6% > 300 µg albumin/mg Cr and 43.9% 30–300 µg albumin/mg Cr). Abnormal proteinuria was seen in the majority of black patients with poorly controlled type 2 diabetes mellitus treated in indigent care clinics. This prevalence may be conservative, due to the widespread use of angiotensin-converting enzyme inhibitor therapy and exclusion of cases treated only by nephrologists. Approximately 70% of black patients with type 2 diabetes cared for in indigent care clinics have abnormal proteinuria and are at heightened risk for ESRD and death.