bluuebunny/crossref_metadata_2025 huggingface dataset:
Micronuclei and Nuclear Abnormalities Observed in Erythroblasts in Myelodysplastic Syndromes and in de novo Acute Leukemia after Treatment
Authors: Yashige H. , Horiike S. , Taniwaki M. , Misawa S. , Abe T.
Published: April 2003

The frequencies of erythroblasts with micronuclei (EBM) and erythroblasts with aberrant nuclear shapes (EBAN) in bone marrow were evaluated in 60 patients with untreated myelodysplastic syndrome (MDS), and also in 21 patients with acute leukemia before and after treatment, and the results were compared regarding cytogenetic patterns. In patients with acute leukemia, the frequencies of EBM and EBAN in bone marrow were 0.60 ± 0.35% (mean ± SD) and 1.2 ± 1.1% before treatment, respectively, the former of which was higher than those obtained from 93 patients with various nonmalignant diseases (p < 0.01). After treatment with antileukemic drugs, the mean values of them significantly increased 9.7 and 6.1 times from the pretreatment ones, respectively. No correlation was found between the yields of EBM and EBAN and cytogenetic patterns, although regimens including administration of vincristine seemed to cause them more frequently. Most patients with MDS showed a consistent increase of EBM and EBAN at the time of diagnosis irrespective of the treatment; the mean frequencies were 7.7 and 6.3 times higher than those obtained from patients with nonmalignant diseases, respectively. Furthermore, the numbers of EBM and EBAN were significantly higher in patients with an abnormal karyotype than those with a normal karyotype (p < 0.05 for EBM and p < 0.001 for EBAN). In particular, 8 patients with a monosomy 7q showed a marked increase of EBAN (4.7 ± 4.4%) and EBAN (13 ± 6.5%). These findings revealed that drastic changes in the morphology of erythroblasts were characteristic features of MDS, and may reflect a disturbance in kinetochore/spindle microtubules, such as endoreduplication, c-mitosis or restitution, in addition to chromosome lagging.
Responses to Single-Dose Thrombopoietin Decrease with Higher Platelet Counts in Mice
Authors: Kelemen Endre , Lehoczky Dezsõ , Jakab Katalin , Bátai Árpád , Vargha Péter
Published: April 2003

Since the description of human thrombopoietin (TPO) we investigated the thrombocytosis-inducing capacity of human serum samples derived from individuals with altered thrombocytopoiesis. Several times the degree of thrombocytosis developing in recipient mice differed markedly even when applying the same human material. In the last 2 years, we applied single doses of recombinant human TPO (rHuTPO) to random-bred CFLP mice, and the same observation was made. Taken together with previous information (before 1970) it was possible to select cases in which the percent increases in circulating platelet counts inversely correlated with the starting levels. It appears, however, that apart from the known absorbing role of platelets and megakaryocytes, the response to single doses of exogenous rHuTPO in mice depends, at least partially, on an unknown endogenous homeostatic mechanism. Mixing thrombopoietically active human sera with platelet-free normal serum in a 1:1 ratio remarkably reduced the thrombocytosis-inducing capacity. Repeated pharmacological doses of TPO, applied in the majority of the reported trials, however, easily obscure the physiological control mechanism.
Response to Granulocyte Colony-Stimulating Factor in an Autoimmune Neutropenic Adult
Authors: Imoto Shion , Hashimoto Makoto , Miyamoto Mitsuko , Murayama Tohru , Murayama Mika , Nakamura Masanori , Matsui Toshimitsu , Chihara Kazuo , Ryo Ryukichi
Published: April 2003

Clinical value of granulocyte colony-stimulating factor (G-CSF) for autoimmune neutropenia (AIN) has not been well established. We experienced an adult case of AIN which showed an excellent response to G-CSF. A 75-year-old female was admitted with high-grade fever. Her neutrophil count was remarkably low (neutrophil 0.09 × 109/l). Antigranulocyte autoantibody was demonstrated in her serum by an immunofluorescence method and she was diagnosed as AIN. Administration of G-CSF (filgrastim 5 μg/kg) gave a rapid increase of neutrophils (from 0.11 × 109/l to 2.10 × 109/l on the second day), which has enabled us to preserve the use of G-CSF for emergency, that is, for overt serious infection.
A Plasma Cell Leukemia Patient Showing Bialleic 14q Translocations: t(2;14) and t(11;14)
Authors: Sonoki T. , Matsuzaki H. , Satterwhite E. , Nakazawa N. , Hata H. , Tucker P.W. , Taniwaki M. , Kuribayashi N. , Harada N. , Matsuno F. , Mitsuya H.
Published: April 2003

We report here an IgG/λ-type plasma cell leukemia patient showing bialleic 14q32 translocations. All immunoglobulins were suppressed in this patient, but a small amount of monoclonal IgG was detected by immunoelectrophoresis. Two cells of six peripheral blood mononuclear cells showed 46,XY,t(2;14)(q11;q32), i(8)(q10), t(11;14)(q13;q32), del(12)(q13.1) by karyotypic analysis. We confirmed the juxtaposition of IgH and PRAD1/Cyclin D1 genes by fluorescent in situ hybridization and overexpression of the PRAD1/Cyclin D1 gene, but Southern analysis showed no bcl-1 rearrangement. We analyzed the t(2;14)(q11;q32) using DNA fragments derived from childhood B-chronic lymphocytic leukemia cases bearing t(2;14)(p13;q32). Southern and Northern analyses demonstrated no alteration of these genes, indicating that this t(2;14) was different from that of childhood B-chronic lymphocytic leukemia. At the IgH loci, Southern analysis showed two rearranged bands and one germ-line band of JH. Cμ was deleted on one rearranged allele but remained on the other, suggesting that the chromosome translocation occurred after productive class switch recombination on the Cμ deleted allele.
Levels of Endothelial, Neutrophil and Platelet-Specific Factors in Sickle Cell Anemia Patients during Hydroxyurea Therapy
Authors: Saleh A.W. , Hillen H.F.P. , Duits A.J.
Published: April 2003

It has been shown that the clinical course of sickle cell (SS) patients can be ameliorated by administration of hydroxyurea (HU). Induction of hemoglobin F (HbF) is thought to be the mechanism responsible for clinical improvement in some patients. However, HU has a variable effect on HbF production and there exists no good correlation between the extent of HbF increase and clinical response. On the other hand, the degree of adherence of SS to vascular endothelium and neutrophil counts correlate well with clinical severity. Being a cytotoxic drug, used in myeloproliferative diseases, HU may alter proliferation among various cell lines. Moreover, HU has been reported to reduce red blood cell (RBC) adhesion receptor expression in young SS individuals and induces changes in endothelial cells in vitro. It should be conceived that in addition to its effects on HbF production, HU may change the clinical symptoms of SS patients by affecting the degree of adherence of different blood cells, by influencing the activity of endothelium as well as the activity of white blood cells (WBC) and platelets. To analyze whether several of the determinants of adhesion are modulated by HU treatment we studied the levels of endothelial activity (soluble vascular adhesion molecule-1, (sVCAM-1), interleukin-8 (IL-8), fibronectin, neutrophil activity (sL-selectin, sIL-6 receptor-α, myeloperoxidase) and platelet activity (von Willebrand factor) in relation to clinical symptoms, hematological data and HbF levels in 8 SS patients before and during 5 months of HU therapy. Steady state sVCAM-1 levels are increased compared to normal controls and a significant decrease is noted during HU treatment, suggesting a decrease in the interactions between RBC and vascular endothelium. The IL-8 levels are comparable to those in normal controls and remain unaffected by HU therapy. Intercurrent infection and crises reveal striking increases in IL-8 which are accompanied by leukocytosis, but otherwise the IL-8 levels do not correlate with hematological data. HU has no demonstrable effect on fibronectin or soluble neutrophil adhesion molecules, but the levels of myeloperoxidase decrease significantly while WBC counts do not, implying a reduction in neutrophil activity which may help attenuate the propagation phase of a vasoocclusive crisis.
Homozygous Prothrombin Gene Mutationand Ischemic Cerebrovascular Disease
Authors: Giordano Paola , De Lucia Domenico , Coppola Brigida , Iolascon Achille
Published: April 2003

We report the case of a 31-year-old woman who, at the age of 26 suffered from an episode of superficial thrombophlebitis in the left leg, experienced two episodes of transient ischemic attacks at the age of 30 and had an ischemic stroke with left-sided hemiparesis at the age of 31 years. A cerebral CT scan showed an ischemic lesion in the right sylvian area involving the opercular and nucleocapsular regions. Her father had had an ischemic stroke at the age of 54 years and died at the age of 58; her mother had had a myocardial infarction at the age of 48 years and died at 51 years from breast cancer. Laboratory investigation of the patient demontrated high levels of fibrinogen, F II, F VII, F 1 + 2, FPA and ACA-IgG with low levels of HDL cholesterol associated with homozygosity for the 20210 A genotype. There were no other genetic or acquired prothrombotic defects. In conclusion, this case strongly suggests a clinically significant role ot the prothrombin gene mutation in both arterial and venous thrombosis.
What Is the Definition of Cure for Aplastic Anemia?
Authors: Camitta Bruce M.
Published: April 2003

Treatment with immune suppression and bone marrow transplantation has improved the response rates and survival of patients with aplastic anemia. Measurement of response requires that common endpoints be recorded at specific times. There has been no agreement on such parameters for patients with aplastic anemia. In this paper issues related to measurement of response are reviewed and criteria for response are proposed. Adoption of uniform criteria would facilitate comparisons of treatment efficacy.
Comparative Genomic Hybridization Study of de novo Myeloid Neoplasia
Authors: Castuma María V. , Rao Palavarthy H. , Acevedo Susana H. , Larripa Irene B.
Published: April 2003

Comparative genomic hybridization (CGH) was used to detect chromosomal imbalances in 20 patients with a diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). The results obtained were compared with G-banding analysis. This last methodology showed 50% of cases with clonal abnormalities whereas CGH detected 70% of cases with copy number changes. Gains were more frequent than losses and constituted 66% of total changes detected. The most common gains included chromosomes 21 and chromosome region 18p for AML and chromosome 17 and region 1p33p35 for MDS. Losses represent 34% of changes and the regions involved were 5q31q32, 7q22, 7p12 and 13q21q22. CGH revealed additional chromosome imbalances in 12 of 20 cases (60%) which were not detected by traditional cytogenetic studies, demonstrating complex karyotype in 50% (6/12). Combination of CGH and G-banding provides an efficient method to identify critical regions present in the malignant clone, which is of great value in the prognosis and outcome of myeloid neoplasias.
Intravenous Calcitriol Improves Anaemia and Reduces the Need for Erythropoietin in Haemodialysis Patients
Authors: Goicoechea M. , Vazquez M.I. , Ruiz M.A. , Gomez-Campdera F. , Perez-García R. , Valderrábano F.
Published: April 2003

In cases with severe hyperparathyroidism, anaemia improves after parathyroidectomy. The objective of this study was to investigate the influence of treatment with intravenous calcitriol on anaemia in 28 haemodialysis patients. The patients showed moderate to severe hyperparathyroidism (mean parathyroid hormone level 811.6 ± 327 pg/ml) and were treated with calcitriol (2 µg i.v.) after haemodialysis. The follow-up period was 12 months. 21 out of the 28 patients had been receiving erythropoietin (EPO) prior to calcitriol administration; the remaining 7 did not receive EPO. 24 patients received oral or intravenous iron. The doses of EPO and iron were modified throughout the study period to maintain a haematocrit equal to or higher than 30% and ferritin levels above 150 ng/ml, respectively. EPO needs were evaluated according to the relation EPO dose/haematocrit. We found a significant rise in haematocrit and haemoglobin at 3 and 12 months on calcitriol therapy, with no modification of the EPO dose nor ferritin levels. This improvement in anaemia was observed both in those patients who received EPO initially (p < 0.01) and in those who did not (p < 0.05). Upon dividing the patients according to the response of hyperparathyroidism to the intravenous calcitriol treatment, we observed in the responding patients (n = 19) significant increases in haematocrit (from 31.7 ± 4.2 to 36.3 ± 4.9%) and haemoglobin (from 10.6 ± 1.5 to 12.2 ± 1.5 g/dl; p < 0.001) at 12 months on intravenous calcitriol therapy, while this was not true of the non-responding patients. The EPO needs diminished in the group of responding patients and increased in the non-responders, although these changes were not statistically significant. We found no direct correlation between the decrease of parathyroid hormone and EPO needs in the group of responding patients. However, an inverse correlation between parathyroid hormone levels and EPO needs (r = –0.799, p < 0.05) was seen in the group of non-responding patients. Treatment with intravenous calcitriol in patients on haemodialysis controls secondary hyperparathyroidism, improves anaemia, and decreases the need for EPO. Studies including a larger number of patients are necessary to clarify the mechanisms underlying the improvement of anaemia upon control of secondary hyperparathyroidism with intravenous calcitriol treatment and to confirm our findings.
Prevalence of Cholelithiasis in Non-Diabetic Haemodialysis and Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Korzets Z. , Golan E. , Ben-Chitrit S. , Schneider N. , Chagnac A. , Carel R. , Bernheim J.
Published: April 2003

Haemodialyzed (HD) patients have been found to have an increased bile cholesterol level and an increased saturation index in bile. These changes were markedly enhanced in the presence of a low-protein diet. To evaluate whether such changes influence the prevalence of cholelithiasis in patients with end-stage renal failure, real-time sonography was performed to detect the presence of gallstones (GS) in 54 HD (28 males, 26 females, mean age 52.4 ± 15.4 years) and 39 continuous ambulatory peritoneal dialysis (CAPD; 22 males, 17 females, mean age 59.1 ± 14.9 years) patients. No patient had diabetes. The patients’ charts were reviewed for the following data: age, sex, primary renal disease, obesity (20% above ideal weight), history suggestive of gallbladder disease or previous cholecystectomy, duration of dialysis, and serum cholesterol levels. Overall, cholelithiasis was documented in 12 of 93 (12.9%) patients, 7 HD and 5 CAPD. When comparing the factors outlined above, no significant difference was found between HD and CAPD patient groups, either with or without cholelithiasis. Gallbladder disease was asymptomatic in all except 1 patient who required cholecystectomy. Using a healthy control group consisting of local age- and sex-matched inhabitants, GS were found in 8 of 134 (6%) of them (p > 0.05). We conclude that the prevalence rate of GS in our dialysis population (HD and CAPD) is similar to that of a local general population following a western-style diet, irrespective of dialysis mode.
Localization of Parathyroid Glands in Hemodialysis Patients Using Tc-99m Sestamibi Imaging
Authors: Ishibashi Masatoshi , Nishida Hidemi , Okuda Seiya , Suekane Shigetaka , Hayabuchi Naofumi
Published: April 2003

Tc-99m sestamibi parathyroid imaging was performed in 28 patients with chronic renal failure to localize abnormal parathyroid glands in patients receiving hemodialysis, and compared the localization with ultrasonography and magnetic resonance (MR) imaging. Methods: We imaged 28 patients with secondary hyperparathyroidism using Tc-99m sestamibi (about 600 MBq) at 10 min and 2–3 h following radiotracer injection. In addition, mediastinal images were recorded at approximately 1 h following injection to identify ectopic parathyroid glands. All patients also were evaluated with ultrasonography and MR imaging. Results: Tc-99m sestamibi scans demonstrated focal uptake in 60 glands of the 28 patients, and was categorized as slight uptake in 71.7% (43/60), and intense uptake in 28.3% (17/60). Seventeen of the 28 patients underwent parathyroidectomy. A total of 64 glands were resected. Sestamibi imaging was more sensitive for localizing abnormal parathyroid glands than ultrasonography or MR imaging. Histologic evaluation of 27 resected parathyroid glands revealed that the number of oxyphil or chief cells was not proportional to sestamibi uptake. Conclusion: Our data indicate that Tc-99m sestamibi imaging should be used initially to localize abnormal parathyroid glands in hemodialysis patients with secondary hyperparathyroidism, prior to MR imaging or ultrasonography. Sestamibi uptake in parathyroid glands may not correlate with the degree of hypercellularity of oxyphil cells.
Ultrastructural Study of Anionic Sites in Glomerular Basement Membranes at Different Perfusion Pressures by Quick-Freezing and Deep-Etching Method
Authors: Yu Ying , Leng Chong-Guang , Kato Yasuko , Terada Nobuo , Fujii Yasuhisa , Ohno Shinichi
Published: April 2003

The ultrastructures of anionic sites in rat glomerular basement membranes (GBM) were studied at different perfusion pressures of 100, 150, 200 or 250 cm H2O by a quick-freezing and deep-etching (QF-DE) method, in addition to conventional fixation methods, using polyethyleneimine (PEI) as a cationic tracer. By the QF-DE method, three-dimensional ultrastructures at each pressure were observed more clearly than those seen on conventional ultrathin sections. When the perfusion pressures were changed from low levels to higher ones, the total thickness of GBM with anionic sites became gradually thinner. Many PEI particles were observed around filaments, not only in the laminae lucidae, but also in the lamina densa. These findings indicated the existence of anionic sites in both laminae lucidae and lamina densa of GBM. The numbers of PEI particles in the lamina rara externa were counted on conventional ultrathin sections for morphometric analyses. The numbers per unit length of GBM were significantly decreased at higher perfusion pressures (200 and 250 cm H2O) than those seen at both normal (150 cm H2O) and lower (100 cm H2O) pressures. It is concluded that the ultrastructures of anionic sites in the GBM may be changed in vivo, depending on the hemodynamics in the glomerular capillary.
Physical Factors and Glomerulosclerosis
Authors: Wesson L.G.
Published: April 2003

Glomerulosclerosis (GS) designates a pathological process within the glomerulus of some and perhaps all mammalian species. Laboratory rats and man have been the most studied. GS is characterized at the outset by increase in volume of the glomerular matrix of one, several or many lobules of the tuft of glomerular capillaries. This process progresses usually in association with proliferation of the mesangial cells of the affected glomerulus. The process ends with collapse of the glomerular capillaries and obliteration of Bowman’s space. In the absence of other pathology GS progresses relatively slowly, becoming evident first in a few glomeruli, the numbers increasing until as many as half or more may be found in various stages of sclerosis in the mature or old animal. Proteinuria is present and proportional to the number of affected glomeruli and the intensity of involvement.
Soluble P-Selectin Is Released from Activated Platelets in vivo during Hemodialysis
Authors: Kawabata Kenji , Nagake Yoshio , Shikata Kenichi , Fukuda Shinji , Nakazono Hiroshi , Takahashi Maki , Ichikawa Haruo , Makino Hirofumi
Published: April 2003

During hemodialysis, platelets are activated across a dialyzer. Soluble P-selectin (sP-selectin) is a form of P-selectin which is a glycoprotein relocated from secretory granules to the surfaces of platelets and endothelial cells after these cells have been physiologically activated. To investigate whether sP-selectin is useful as a marker of platelet activation during hemodialysis, we measured the plasma concentration of sP-selectin by enzyme-linked immunosorbent assay in 6 patients hemodialyzed in our institute using regenerated cellulose (RC) membranes and thereafter polysulfone membranes. Concomitantly, we also measured the plasma concentration of platelet factor 4 and β-thromboglobulin which are released from α-granules of activated platelets. During hemodialysis with RC membranes, the β-thromboglobulin level was significantly increased 15 min (p < 0.05) and the sP-selectin level 15 (p < 0.05) and 180 min (p < 0.05) after initiation of dialysis on the venous side as compared with the arterial side of the hemodialyzer. During hemodialysis with polysulfone membranes, no significant variation in plasma β-thromboglobulin and sP-selectin levels was detected. The platelet factor 4 level increased more significantly across a dialyzer 180 min after initiation of dialysis with RC than with polysulfone membranes (p < 0.01). The changes in plasma platelet factor 4 and β-thromboglobulin levels demonstrated that platelets are more activated during hemodialysis with RC than with polysulfone membranes. The changes in plasma sP-selectin levels during hemodialysis with RC confirm that the release of P-selectin purely from activated platelets was detected by enzyme-linked immunosorbent assay. sP-selectin may be a marker of platelet activation during hemodialysis.
Serial Alterations of Glomerular Matrix-Degrading Metalloproteinase Activity in Anti-Thymocyte-Induced Glomerulonephritis in Rats
Authors: Sato Yuji , Fujimoto Shouichi , Hamai Keiko , Eto Tanenao
Published: April 2003

In the present study, we investigated the serial changes of glomerular metalloproteinase (GMP) activity in antithymocyte-induced glomerulonephritis (Thy.1 GN) in rats. GMP activity was determined by the measurement of EDTA-inhibitable gelatinolytic activity toward tritiated gelatin as substrate. Thy.1 GN was made by injection of antithymocyte serum into female Wistar rats and glomeruli were separated by a graded sieving method. Glomeruli were homogenized with sonication, and then the supernatant was used for the assay of GMP activity and substrate study. GMP activity was reduced on day 1 and at week 2 compared with controls, and returned to the control level by week 9. On light-microscopic examination, diffuse and focal glomerular ECM expansion were observed at weeks 2 and 4, respectively. These changes disappeared by week 9. With the use of several substrates labeled with tritium, GMP was observed to degrade type IV collagen, fibronectin and casein as well as gelatin, but not type I collagen. In conclusion, attenuated GMP activity may be one of the causes of glomerular ECM expansion in Thy.1 GN, because GMP was capable of degrading the components of glomerular ECM.
A Case of Chronic Graft-versus-Host Disease following Living-Related Donor Kidney Transplantation
Authors: Ohtsuka Yoko , Sakemi Takanobu , Ichigi Yasuhisa , Tanaka Tatsurou , Nakamura Koji
Published: April 2003

A 25-year-old man with a 2.5-year history of maintenance hemodialysis underwent a living-related donor (father) kidney transplantation. He was free from acute rejection, but 8 months after the kidney transplantation, he complained of malaise and fever which were accompanied by eruptions on the face, fingers, and hips which resembled symptoms seen in patients suffering from systemic vasculitis. Skin biopsy findings were compatible with those of chronic graft-versus-host disease (GVHD). The human leukocyte antigen (HLA) family study disclosed that the donor’s HLA haplotype was homozygous and identical to one of the recipient’s HLA haplotypes which indicated that the host would not resist engraftment. On the basis of these findings, a diagnosis of chronic GVHD was made, and increasing doses of immunosuppressants resulted in a resolution of these symptoms. Our report is the first describing GVHD that developed in a patient undergoing related-donor kidney transplantation.
Lymphocyte Subsets in Hemodialyzed HCV+ and HCV– Patients
Authors: Cucciaioni S. , Pellegrini L. , Giombini L. , Buoncristiani U. , Tacconi P. , Vatteroni M.L. , Bruschi F.
Published: April 2003

The aim of our study was to get information on the immune status of patients who undergo haemodialysis in the presence of an HCV infection. This virus infects not only hepatocytes, but also blood mononuclear cells, in particular B cells [1], but we do not know the role of this lymphocyte involvement in the maintenance and progression of hepatitis. The impairment of the cell-mediated immune response in uraemic patients is well known, for example only 50–60% of uraemic patients undergo a seroconversion after HBV vaccine, compared to 95% of the normal population. Paradoxically the immunodeficiency is concomitant with an activation of related cells which is increased rather than ameliorated by the dialysis treatment [2]. In these patients lymphocytopenia is also present with a reduction of the absolute number of T lymphocytes which remain normal in percentage. The study was performed on the following groups of subjects.
More about Acyclovir Neurotoxicity in Patients on Haemodialysis
Authors: Gómez Campderá F.J. , Verde E. , Vozmediano M.C. , Valderrábano F.
Published: April 2003

Acyclovir is an efficient treatment in virus infections of the herpes family. Now that it has been in use for more than 10 years, neurotoxicity is a well-known complication, especially after the intravenous use [1]. However, recently cases of neurotoxicity after the oral use in patients with terminal renal failure (TRF) on haemodialysis (HD) have been described [2–5]. This has been associated with high serum levels of the drug, representing an overdose and a significant modification of the dosage has been recommended in these patients [2, 4, 5]. HD has been shown to be an efficient method of elimination as well as a diagnostic method to differentiate between acyclovir neurotoxicity and encephalitic herpes [6].
Anti-Thymocyte Globulin Therapy in a Patient with pANCA Vasculitis and Crescentic Glomerulonephritis
Authors: Lukas Renate , Keller Frieder
Published: April 2003

Standard treatment of systemic vasculitis with rapidly progressive glomerulonephritis consists of steroid pulses, oral prednisolone and cyclophosphamide [1]. For cases requiring haemodialysis, additional plasma exchanges have been recommended [2]. Antibody therapy has been proposed for refractory vasculitis as a compassionate treatment [3, 4].
Three-Year Outcome afterUrinary Diversions in Patients with Obstructive Uropathy
Authors: Takeda Kazuhito , Harada Atsumi , Hirakata Hideki , Fujimi Satoru , Oh Yukinori , Fujishima Masatoshi
Published: April 2003

Obstructive uropathy accounts for less than 5% of all instances of acute renal failure [1] and the causes are genitourinary tract malignancies, benign prostatic hypertrophy, urolithiasis, or retroperitoneal mass, and it is more common in the elderly [2–4]. The clinical courses progressing to an established renal failure are known to be either rapid or insidious, depending on the duration to the completion of the bilateral urinary tract obstruction. Urinary diversions such as nephrostomy or retrograde ureteral catheterizations are effective and the renal function usually recovers with a marked diuresis [5, 6]. The mortality rate is reported to be 50% at 3 months or 90% at 1 year in cases of malignancy-induced obstructive uropathy [7, 8].
Improvement of Nutritional Status in Patients Receiving Maintenance Hemodialysis after Correction of Renal Anemia with Recombinant Human Erythropoietin
Authors: Tarng Der-Cherng , Huang Tung-Po , Doong Tsuey-Ing
Published: April 2003

Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 ± 0.8 g/dl at baseline to 10.7 ± 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 ± 7.5 to 23.6 ± 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.
Accidental Aluminum Intoxication in Patients Undergoing Acetate-Free Biofiltration
Authors: Hdez-Jaras J. , Galán A. , Sánchez P.
Published: April 2003

Eight patients undergoing acetate-free biofiltration (AFB) suffered aluminum intoxication. The source of this outbreak was parenteral exposition to high concentrations of aluminum in sodium bicarbonate solutions. The manufacturer of bicarbonate solutions used in AFB was substituted in May 1994 and the solutions were stored in glass containers. At the peak of intoxication (July 1994) serum aluminum determination revealed an average value of 147.3 ± 21 µg/l. Aluminum levels in bicarbonate solutions were 400 µg/l. Serum ferritin rose from 307.4 ± 161 to 735.6 ± 206 ng/ml, whereas MCV decreased significantly from 98.4 ± 9 to 90.1 ± 10 fl. No significant changes were found in hemoglobin, neither in plasma iron, nor in iron transferrin saturation. The doses of recombinant human erythropoietin showed a considerable increase. The replacement solutions were changed and a new solution, stored in plastic containers and with aluminum levels lower than 10 µg/l, was used. The biochemical parameters were normalized. This outbreak demonstrates the need for a stringent control of aluminum-containing replacement fluids.
Development of Calcium Oxalate Crystals on Urothelium: Effect of Free Radicals
Authors: Grases F. , García-Ferragut L. , Costa-Bauzá A.
Published: April 2003

The effects of free radicals on the development of crystals attached to the living epithelium have been studied using an experimental model that enables close simulation of the conditions prevailing in the kidney. The results obtained clearly demonstrate that free radical-damaged cells produce a favorable environment for crystal development. At low free radical concentrations, crystals develop on calcium-enriched zones, whereas at higher concentrations, crystals develop on areas with a destroyed monolayer of superficial cells. Evaluation of the action of some products with antioxidant action and/or crytallization-inhibitory capacity is also included. Antioxidants, such as ascorbic acid and mannitol, exerted the most remarkable effects in avoiding calcium oxalate crystal development, whereas crystal inhibitors, such as citric acid, did not produce any remarkable reduction in calcium oxalate crystallization. Phytic acid notably decreased calcium oxalate crystal development. The ability of phytic acid to diminish calcium oxalate crystallization must be attributed to the combination of its inhibitory capacity of calcium oxalate crystallization and its preventive antioxidant action.
Anti-Idiotype Antibody Directly Interferes with Glomerular IgA Immune Complex Deposition
Authors: Chen Ann , Sheu Lai-Fa , Shaio Men-Fang , Huang Tzu-Hao , Ding Shian-Lin , Lee Wei-Hwa
Published: April 2003

Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB/c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.
Effect of Protamine on Cation-Selective Permeability in Hamster Medullary Thick Ascending Limb of Henle’s Loop
Authors: Koyama Shigeru , Yoshitomi Koji , Imai Masashi
Published: April 2003

To estimate the contribution of the paracellular shunt pathway to cation-selective permeability in the hamster medullary thick ascending limb of Henle’s loop, we observed the effect of protamine, a selective blocker of paracellular conductance, on salt-diffusion voltage (dVT) in the isolated nephron segment perfused in vitro. When 300 µg/ml protamine was added to the lumen, the lumen-positive dVT generated upon reduction of the lumen NaCl concentration was decreased from 5.1 ± 0.9 to 0.8 ± 0.8 mV and the calculated Na+/Cl– permeability ratio was decreased from 1.40 ± 0.14 to 0.86 ± 0.08. Although the effect of protamine persisted after removal of the agent from the lumen, addition of 30 U/ml heparin, which neutralizes protamine, returned the dVT toward the control level. This effect was almost the same when the orientation of the imposed NaCl gradient was reversed. Protamine exhibited a similar effect on dVT in the presence of ouabain added to the bath. Protamine was without effect from the bath. Protamine did not affect the basel VT perfused with the control solution. Increased VT by decreasing perfusion pressure was inhibited by adding protamine from the lumen. These observations suggest that the paracellular pathway contributes to the cation selectivity of the medullary thick ascending limb. The cation selectivity of the paracellular shunt pathway may mainly account for the changes in VT which are either dependent on the luminal flow rate or transmural NaCl concentration gradient, while it may not contribute to the basal level of VT.
Effect of Increased Hemodialysis Dose on Endogenous Erythropoietin Production in End-Stage Renal Disease
Authors: Ifudu Onyekachi , Friedman Eli A.
Published: April 2003

We investigated 20 patients (12 men and 8 women) with end-stage renal disease sustained on hemodialysis to determine the effect of 6 weeks of increased dialysis dose on endogenous erythropoietin production. Increased dialysis dose was achieved by increasing thrice-weekly dialysis treatment time from 4 to 4.5 h and switching from an MCA 160 dialyzer to an F80 dialyzer. The mean age of the study subjects was 51 ± 13.8 years, and the mean duration of end-stage renal disease prior to the study was 31.4 ± 55.5 months. All subjects were receiving recombinant erythropoietin for at least 4 months prior to the study. The dialysis dose was increased from a mean reduction of urea of 60.7 to 72%. At baseline, the group’s mean hematocrit was 28.4 ± 3.4%, the mean predialysis endogenous erythropoietin level was 9.1 ± 4.5 (range 2.5–18.4) mU/ml, the mean reduction of urea was 60.7 ± 4%, and the mean transferrin saturation was 22.6 ± 15.5%. Mean thrice-weekly recombinant erythropoietin injections were administered intravenously after dialysis to each patient at a dose of 51 ± 19 U/kg body weight. After 6 weeks of an increased dialysis dose, the mean hematocrit increased from 28.4 ± 3.4 to 32.3 ± 3.3% (p = 0.0001), while the mean serum endogenous erythropoietin level decreased from 9.1 ± 4.5 (range 2.5–18.4) mU/ml to 6.1 ± 3.2 (range 2.5–13.4) mU/ml (p = 0.0001). We conclude that the serum endogenous erythropoietin levels decrease with increased dialysis dose and that the increase in hematocrit following increased dialysis dose is probably not mediated by changes in endogenous erythropoietin.
Eradication and Follow-Up of Helicobacter pylori Infection in Hemodialysis Patients
Authors: Muñoz de Bustillo E. , Sánchez Tomero J.A. , Sanz J.C. , Moreno J.A. , Jiménez I. , López-Brea M. , Pajares J.M. , Traver J.A.
Published: April 2003

It is currently accepted that Helicobacter pylori (Hp) infection is crucial in the pathogenesis of peptic ulcer. Therefore, we developed a prospective study to assess the prevalence of Hp infection by the 13C Urea Breath Test (13C UBT) in 52 hemodialysis patients, and we evaluated the efficacy of two consecutive eradication regimens in 23 positive patients with dyspepsia and/or on a transplantation list. The correlation between anti-Hp serology and 13C UBT results was also analyzed in 34 patients who were followed up during 18 months. The Hp prevalence by 13C UBT was 63.5% (33/52). The eradication rate after the first cycle of therapy (amoxicillin 500 mg/8 h and omeprazole 20 mg/12 h, 14 days) was 60.8% (14/23). After the second cycle (clarithromycin 500 mg/ 12 h plus omeprazole 20 mg/12 h, 14 days), the eradication rate reached 82.6% (19/23). The serological procedure showed a good correlation with 13C UBT (about 80% sensitive and specific) when very restrictive diagnostic and eradication criteria were adopted. We conclude that an eradication rate higher than 80% can be reached after two consecutive cycles of dual therapy in hemodialysis patients. Anti-Hp serological tests must be cautiously interpreted in these patients.
Effect of Glucose on Matrix Metalloproteinase Activity in Mesangial Cells
Authors: McLennan Susan V. , Yue Dennis K. , Turtle John R.
Published: April 2003

Mesangial cells are known to secrete matrix metalloproteinases (MMPs). These enzymes play a major role in the degradation and remodelling of extracellular matrix, and alterations in their activity may contribute to the mesangium enlargement of diabetic nephropathy. MMPs are secreted as latent forms which are cleaved in the pericellular environment to form active enzymes. In this study, we used a biosynthetically labelled matrix as substrate and conditioned medium obtained from mesangial cells, as a source of enzymes to investigate the effect of a high glucose concentration on degradative capacity. Inhibitor studies showed that MMPs were responsible for 72.2% of the degradation. A high glucose concentration caused a significant reduction in matrix degradation (low glucose 33.5 ± 5.6%, high glucose 24.2±4.8%). Addition of aminophenyl mercuric acetate to activate latent MMPs increased matrix degradation by 2.3-fold in both low- and high-glucose media, but the decreased degradation caused by a high glucose concentration was still apparent. Activation with plasmin also increased matrix degradation and abolished the effect of the high glucose concentration. Gelatin zymography showed that mesangial cells grown at a low glucose concentration secreted both 72- and 92-kD gelatinases; however, at high glucose concentrations the 92-kD gelatinase was no longer apparent. These results suggest that a high glucose concentration causes a reduction in the amount of MMPs secreted by the mesangial cells. This reduction may contribute to the mesangium enlargement of diabetic nephropathy.
Apoptosis of Tubular Epithelial Cells in Familial Juvenile Gouty Nephropathy
Authors: Lhotta Karl , Gruber Johann , Sgonc Roswitha , Fend Falko , König Paul
Published: April 2003

Two patients, a 47-year-old woman suffering from chronic renal failure, hyper- uricemia and gout, and her 26-year-old son with hyperuricemia and chronic renal failure, are described. The father and two siblings of the woman had died of chronic renal failure. Both patients had a markedly reduced fractional excretion of urate, which was significantly increased by both benzbromarone and probenecid. A renal biopsy of the son revealed an unspecific chronic tubulointerstitial nephropathy. By light microscopy, many proximal tubular epithelial cells showed signs of apoptosis, which was confirmed with the specific TUNEL assay. We propose a hypothesis based on a gain-of-function mutation of the luminal anion exchanger of the proximal tubulus to explain reduced uric acid excretion, dominant inheritance and apoptosis of tubular epithelial cells in this rare disease. Treatment with a combination of allopurinol to reduce the renal urate load and benzbromarone to block the tubular anion exchanger and normalize fractional uric acid excretion is suggested.
Serum Levels of Soluble Adhesion Molecules in Chronic Renal Failure and Dialysis Patients
Authors: Bonomini Mario , Reale Marcella , Santarelli Patrizia , Stuard Stefano , Settefrati Nicola , Albertazzi Alberto
Published: April 2003

Besides cell-bound adhesion molecules, which are of fundamental importance to a large number of physiological and pathological processes, soluble forms of adhesion molecules have been detected in the circulating blood in recent years. Circulating soluble adhesion molecules appear to be biologically active, and raised levels have been reported in a variety of disorders. In the present study, we used ELISA to measure the serum levels of four soluble adhesion molecules in 23 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 17 on chronic hemodialysis (HD) and 18 healthy controls having a similar mean and distribution of ages. The investigated soluble (s) molecules included intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin and sP-selectin. sICAM-1 was found to be elevated in patients with CRF (p < 0.05), on CAPD (p < 0.02) and HD (p < 0.0001) compared with the controls but levels did not differ between the three patient groups. The higher sVCAM-1 values found in CRF (p < 0.02), CAPD (p < 0.05) and HD (p < 0.0001) as compared to controls again failed to differentiate the three groups of patients. Soluble E-selectin was also raised in the three groups (p < 0.0001) with no difference between them. Increased sP-selectin was found in CRF (p < 0.05), CAPD (p < 0.02) and in HD patients (p < 0.0001) compared to controls, and levels in HD were significantly higher (p < 0.02) than in CRF patients. Predialysis serum molecule levels did not differ between HD patients treated with cuprophan or with polyacrylonitrile dialyzers. HD sessions with both dialyzers had no effect on sICAM-1, while a decrease (p < 0.02) in sP-selectin was found after dialysis with cuprophan. In undialyzed patients with CRF, regression analysis showed a strong linear correlation between serum creatinine and serum levels of each soluble molecule. These results demonstrate that serum levels of soluble adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin are elevated in both undialyzed patients with CRF and patients on CAPD or HD. The elevated serum levels of these proteins probably reflect inadequate clearance as well as enhanced synthesis/release.
Prevalence of Hepatitis G Virus Infection in Slovenian Hemodialysis Patients as Determined by the Detection of Viral Genome and E2 Antibodies
Authors: Seme Katja , Poljak Mario , Jeverica Samo , Koren Anja , Saša Žužek-Rešek S.
Published: April 2003

The prevalence of hepatitis G virus (HGV) infection was assessed by the detection of viral genome and HGV E2 antibodies in hemodialysis patients from a dialysis unit with the highest prevalence of hepatitis C virus infection in Slovenia. HGV RNA was detected in 7 (11.9%) and HGV E2 antibodies in 20 (33.9%) of 59 hemodialysis patients. One patient had detectable HGV RNA as well as HGV E2 antibodies in her serum sample at the time of the study. The total prevalence of HGV infection was 44.1%. Our results clearly indicate that the mere detection of HGV RNA in serum samples would seriously underestimate the real prevalence of HGV infection in hemodialysis patients. Therefore, when assessing the prevalence of HGV infection in hemodialysis patients, detection of both antibody and nucleic acid is requisite.
Percutaneous Renal Biopsy in Children: A 27-Year Experience
Authors: Feneberg R. , Schaefer F. , Zieger B. , Waldherr R. , Mehls O. , Schärer K.
Published: April 2003

Background: The introduction of automated biopsy devices and the localization of the kidney by ultrasound were aimed at optimizing efficacy and safety of the percutaneous renal biopsy procedure. We evaluated these technological advances in our renal biopsies performed in children. Methods: We sequentially used the Silverman needle (1969–1974), the TruCut needle (1974–1990), and the automated Biopty device (1990–1996). Fluoroscopy was used to localize the kidney until 1985, ultrasound examination prior to biopsy from 1985 to 1992, and direct ultrasound guidance since 1992. A total of 962 native kidney biopsies and 119 allograft biopsies were performed. Results: In the native kidney biopsies, the introduction of the Biopty device and ultrasound guidance were independently associated with fewer passes required to obtain adequate tissue and more glomeruli per specimen. The rate of biopsies yielding more than 9 glomeruli increased from 69 to 92% (p < 0.05). The number of glomeruli harvested per centimeter core length was inversely related to patient age (p < 0.01). More appropriate cortical tissue was retrieved in renal allograft biopsy specimens with the application of the new techniques. The occurrence of macroscopic hematuria (9.6%) in the native kidney biopsies was not affected by the puncture or localization technique applied, but subcapsular hematomas were documented more often with the Biopty device (42%) than with the TruCut needle (16%), probably due to improved ultrasound equipment. In the whole series 2 patients died, and 3 others required renal surgery and 4 blood transfusions. Conclusions: The automated ultrasound-guided procedure is a feasible and reliable technique for percutaneous renal biopsy in children. It gives a greater yield of diagnostic tissue without increasing the rate of clinical complications.