bluuebunny/crossref_metadata_2025 huggingface dataset:
ALK-Negative Anaplastic Large Cell Lymphoma and Hodgkin’s Disease of Nodular Sclerosing Type in 2 Siblings
Authors: Moccia Franca , Tognoni Elisabetta , Boccaccio Piero
Published: April 2003

Familial clustering of Hodgkin’s disease (HD) and increased risk of developing the disease among the siblings of affected patients suggest that both environmental and genetic factors may play an important role in its pathogenesis. An association between Epstein-Barr virus (EBV) and HD has been widely demonstrated. Recently, latent membrane protein of EBV has also been detected in CD30-positive anaplastic large cell lymphoma. Familial aggregation of HD and a three- to seven-fold-increased risk among the siblings of affected patients suggest increased genetically determined susceptibility. No data about genetic factors are available for anaplastic large-cell lymphoma. In this study, the authors report the case of a woman with anaplastic-lymphoma-kinase (ALK)-negative CD30-positive anaplastic large cell lymphoma, whose brother had developed HD 11 years previously. The clinical, histologic, and immunohistochemical features of the 2 lymphomas were studied. Both siblings showed bulky mediastinal involvement, effacement of normal lymph node architecture by large, atypical cells, resembling Reed-Sternberg cells, expression of EBV latent membrane protein-1 in the lymph node specimens, concordance of both HLA classes I and II. The clinical presentations and immunological studies disclose numerous similarities between the 2 cases and can suggest that their association is not fortuitous. At present, in problematic cases, a combination of morphologic, immunophenotypic and genetic studies may contribute to better define the tumour type.
Effects of Renal Perfusion Pressure on Renal Interstitial Hydrostatic Pressure and Na+ Excretion: Role of Endothelium-Derived Nitric Oxide
Authors: Nakamura Tetsuya , Alberola Antonio M. , Salazar F. Javier , Saito Yuichiro , Kurashina Toshiaki , Granger Joey P. , Nagai Ryozo
Published: April 2003

The purpose of this study was to examine the role of endothelium-derived nitric oxide in modulating the effect of renal perfusion pressure (RPP) on renal interstitial hydrostatic pressure (RIHP) and urinary Na+ excretion (UNaV). The effects of RPP on renal hemodynamics, RIHP, and Na+ and Li+ excretions were determined in control Sprague-Dawley rats, in Sprague-Dawley rats pretreated with intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) at doses of 1, 5, and 50 µg/kg/min, and in rats pretreated with L-NAME (5 µg/kg/min) plus L-arginine (10 mg/kg/min). The RPP was changed from 95 to 135 mm Hg by an electronically servo-controlled aortic occluder above the renal arteries in all groups. Increasing RPP in control rats from 95 to 135 mm Hg increased RIHP (from 4.4 ± 0.5 to 8.7 ± 1.2 mm Hg), UNaV (from 2.37 ± 0.61 to 8.29 ± 1.59 µEq/min), and fractional excretion of Li+ (from 38.0 ± 2.5 to 51.4 ± 6.0%). In rats pretreated with L-NAME (5 µg/kg/min), increases in RPP from 95 to 135 mm Hg had no effect on RIHP (from 1.6 ± 0.4 to 2.2 ± 0.6 mm Hg) or fractional excretion of Li+ and markedly attenuated pressure-natriuresis relationship (from 1.84 ± 0.50 to 2.88 ± 0.65 µEq/min). Although L-NAME did reduce renal plasma flow and glomerular filtration rate, the autoregulatory responses to RPP were maintained. In rats pretreated with L-NAME plus L-arginine, RIHP, UNaV, and fractional excretion of Li+ responses to RPP were similar to the control rats. The results of this study indicate that endothelium-derived nitric oxide plays an important role in modulating the effect of RPP on Na+ excretion by enhancing the transmission of RPP into the renal interstitium.
Adequate Management of Heparin-Associated Thrombocytopenia
Authors: Fischer Karl-Georg , Schollmeyer Peter
Published: April 2003

In a recent issue of Nephron Berlot and Lucchese [1] reported their management of heparin-associated thrombocytopenia (HAT) during continuous venovenous hemofiltration. They described a case of rapid onset of severe thrombocytopenia after initiating intravenous heparin therapy and stated ‘that the diagnostic criteria for HAT have been completely fulfilled’. Despite of that, they reported a continuation of heparin therapy at lower doses without recovery of platelet counts at that stage and at last the slow return of platelet counts into the normal range more than 1 week after finishing intravenous heparin therapy. With reference to the current literature and the clinical experience in our hospital, this approach does not seem to be adequate.
Correlation between Urinary Epidermal Growth Factor Excretion and Serum Thyroid Hormone in Premature and Term Neonates
Authors: Tsau Yong-Kwei , Teng Ru-Jeng , Chen Chiung-Hui
Published: April 2003

Eighty neonates, including 14 full-term, 31 premature, 27 twin or triplet, 6 small-for-gestational-age, and 2 infants with hyperthyroidism, were evaluated. The urinary epidermal growth factor/creatinine ratio (EGF/Cr) on the 1st postnatal day was not statistically different among full-term, premature, multiple-pregnancy, and small-for-gestational-age infants (F = 1.06, p = 0.6). There was no difference in urinary EGF/Cr between the 1st postnatal day and the 7th day (p = 0.4 by paired t test). The urinary EGF/Cr was not correlated with the serum thyroid-stimulating hormone level (r = –0.162, n = 60, p = 0.21), but showed a positive correlation with serum total T3 (r = 0.526, n = 60, p < 0.001) and with serum total T4 (r = 0.460, n = 60, p < 0.001). The correlation between urinary EGF/Cr and serum free T4 was even much better (r = 0.727, n = 25, p < 0.001). These results implicate that thyroid hormone may play a role in regulating urinary EGF excretion.
Retroperitoneal Fibrosis with Perinuclear Antineutrophil Cytoplasmic Antibodies and a Longitudinally Extended Periaortic Soft-Tissue Structure on CT
Authors: Sakemi Takanobu , Tomiyoshi Yoshiyuki , Yano Hiromi , Ikeda Yuji , Matsuo Yoshitomo , Kudo Sho
Published: April 2003

A 63-year-old woman showed positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) and presented with an interesting CT finding of a periaortic soft-tissue structure seen as a rind of tissue surrounding the aorta, extending longitudinally from descending thoracic aorta to bilateral common iliac arteries which was compatible with an early stage of retroperitoneal fibrosis (RPF). Both pANCA titers and a periaortic mass volume were reduced following corticosteroid treatment. No cases of RPF with a periaortic mass associated with pANCA have been described. Our findings of RPF with pANCA positivity may enlarge the groups of ANCA-associated diseases.
Measurement of Plasma and Urinary Adrenomedullin in Patients with IgA Nephropathy
Authors: Kubo Atsushi , Iwano Masayuki , Minamino Naoto , Sato Hiroaki , Nishino Toshihiko , Hirata Eiji , Akai Yasuhiro , Shiiki Hideo , Kitamura Kazuo , Kangawa Kenji , Matsuo Hisayuki , Dohi Kazuhiro
Published: April 2003

In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3–9) as compared with the group with a low activity (score 0–2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.
Ultrasound-Guided Cannulation of the Internal Jugular Vein for Dialysis Vascular Access in Uremic Patients
Authors: Lin Bing-Shi , Huang Tung-Po , Tang Gau-Jun , Tarng Der-Cherng , Kong Chi-Woon
Published: April 2003

Background: A reliable temporary vascular access is always required for hemodialysis when a permanent vascular access is not available. However, techniques for creating temporary vascular accesses remain imperfect. This study utilized the ‘SiteRite’ ultrasound device to improve both success and complication rates of jugular venous cannulation for temporary access. Methods: This prospective, comparative study recruited 104 uremic patients receiving ultrasound-guided and 86 patients undergoing landmark-guided percutaneous internal jugular venous cannulation of dual-lumen dialysis catheters. Success rate, number of puncture attempts, access time, and the complication rate of the ultrasound technique, in comparison with the landmark-guided technique, were studied. Results: The ultrasound-guided cannulation was superior to the external landmark-guided cannulation in overall success rate (99.0 vs. 86.0%, p < 0.01), success rate of the first puncture attempt (80.8 vs. 34.9%, p < 0.01), average puncture (access) times (15.8 vs. 43.7 s, p < 0.01), puncture trials (1.39 vs. 2.58, p < 0.01), and traumatic complication rate (1.9 vs. 11.6%, p = 0.015). The incidence of infective complications for the ultrasound group was not different from that of the landmark-guided groups (2.9 vs. 2.3%, p = 0.589). Conclusion: The ultrasound-guided technique offers both safety and convenience in inserting jugular venous dialysis catheters. It represents a valuable technique in creating temporary dialysis hemoaccesses.
Nephrotic Syndrome, Hyperreninemia and Multiple Transplant Renal Arterial Stenoses in a Patient with Diabetes
Authors: Wirta O. , Pasternack A. , Mustonen J. , Seppänen S. , Turjanmaa V. , Salmela K. , Helin H.
Published: April 2003

Nine months after cadaveric renal transplantation the nephrotic syndrome developed in a patient with insulin-dependent diabetes. Renal biopsy ruled out tissue lesions induced by cyclosporine, chronic rejection, recurrence of diabetic kidney disease and de novo glomerulopathies. Captopril-enhanced nephrography and a high plasma renin response suggested renal artery disease. Angiography revealed five intrarenal arterial stenoses. Four were successfully dilated with a prompt diuretic response and diminished proteinuria. Late angiography showed a moderate restenosis in two of the dilated arteries. Due to persistent proteinuria, elevated blood pressure and higher serum creatinine levels than at nadir after transplantation low-dose ACE inhibitor therapy was started. This normalized proteinuria, blood pressure and serum creatinine levels. This beneficial response to combined renal artery balloon angioplasty and medical treatment has been sustained for 2.5 years.
The Fibronectin Production Is Increased by Thrombospondin via Activation of TGF-β in Cultured Human Mesangial Cells
Authors: Tada Hisaya , Isogai Sho
Published: April 2003

Thrombospondin (TSP) is a multifunctional glycoprotein that is synthesized by a variety of cells including mesangial cells (MCs). To clarify the effect of TSP on the pathogenesis of diabetic nephropathy, we studied the effect of glucose concentrations on TSP synthesis in cultured human MCs. Thereafter, the effects of TSP on the activation of transforming growth factor beta (TGF-β) and fibronectin production were investigated in MCs. Incubating MCs with elevated glucose levels for 6 days resulted in an increase in TSP synthesis, measured by an enzyme-linked immunosorbent assay, both in culture media and cell layers. Treatment of MCs with TSP (final concentrations 1 and 5 µg/ml) for 24 h resulted in an increase (1.3- and 2.1-fold, respectively) in active TGF-β, which was determined with an enzyme-linked immunosorbent assay using TGF-β-soluble receptor type II, in the culture media without having any effect on the production of total TGF-β. Exposure of MCs to TSP caused enhancement of fibronectin production in both media and cell layers in a TSP dose-dependent manner with the maximum at a TSP concentration of 1 µg/ml. The TSP-induced increase in fibronectin production from MCs was completely prevented by concomitant treatment with 10 µg/ml anti-TGF-β neutralizing antibody. These results indicate that the TSP production is promoted by a high ambient glucose concentration in human MCs and that TSP, in turn, causes an increase in fibronectin production via activation of TGF-β.
Renal CCAAT/Enhancer-Binding Proteins in ExperimentalDiabetes mellitu s
Authors: Zador Ivan Z. , Hsieh Ching-C. , Papaconstantinou John
Published: April 2003

There is evidence that mediators of inflammation including components of the cytokine system are present in human and experimental diabetic kidney disease. CCAAT/enhancer-binding proteins (C/EBPs) represent a family of cytokine-inducible transcription factors. C/EBPs themselves regulate cytokine expression and also the expression of acute-phase reactants and connective tissue proteins. At least three C/EBP isoforms (α, β, δ) are known. Upon stimulation with cytokines or bacterial lipopolysaccharide, the expression of the α isoform typically decreases, and the expression of the β and/or δ isoforms increases. In view of the fact that components of the inflammatory response are present in diabetic kidney disease, there is a potential that the expression and activity of renal C/EBPs are altered in the diabetic state. In this study we sought to examine the status of C/EBP proteins in kidneys of rats with streptozotocin-induced diabetes mellitus. Diabetes was induced in 5 male Sprague-Dawley rats. Eight weight-matched non-diabetic rats were used as controls. Animals were sacrificed after 4 weeks, and the whole kidney nuclear protein was extracted. An electrophoretic mobility shift assay showed that DNA-binding activity was present in all five kidney nuclear extracts of the diabetic animals, but in only 2 out of 8 control samples (p < 0.05). A supershift assay showed that the DNA-bound protein complex consisted mainly of the C/EBPβ isoform. Western analysis showed an increase of the C/EBPβ protein in renal nuclear extracts of the diabetic animals compared to controls (p < 0.05). There was a decrease of the C/EBPα protein in the kidney nuclear extracts of the diabetic animals compared to controls (p < 0.05). We conclude that renal C/EBP dynamics are altered in experimental diabetes mellitus and that the patterns of C/EBP changes resemble those observed after cytokine or lipopolysaccharide stimulation.
End-Stage Renal Disease (ESRD)after Bone Marrow Transplantation: Poor Survival Compar ed to Other Causes of ESRD
Authors: Cohen Eric P. , Piering Walter F. , Kabler-Babbitt Claudia , Moulder John E.
Published: April 2003

Chronic renal failure after successful bone marrow transplantation (BMT) may diminish the quality of life and may also evolve to end-stage renal disease (ESRD) requiring chronic dialysis. Individual reports suggest poor survival of such patients. We evaluated the survival with ESRD after BMT by the case-control method. We found that patients who develop ESRD after BMT have a significantly decreased survival as compared with non-BMT patients. This was true for both diabetic and nondiabetic ESRD (both p < 0.03). These data demonstrate the poor outcome of ESRD after BMT which emphasizes the need for a better understanding of chronic renal failure after BMT.
Reversible Neuropathy in Chronic Renal Failure
Authors: Roy A. , Kalita J. , Gayathri N. , Shankar S.K. , Misra U.K.
Published: April 2003

Chronic renal failure is associated with distal symmetrical axonal neuropathy. We report a 50-year-old man who suffered from chronic renal failure due to benign enlargement of the prostate. He presented with fever and rapidly developing pure motor neuropathy. The nerve conduction velocity was slow and the F response delayed, suggestive of demyelinating neuropathy. A sural nerve biopsy specimen was also consistent with demyelination and axonal changes. This patient improved significantly following intermittent catheterization and a short course of norfloxacin. Renal failure may be associated with reversible motor neuropathy.
i-STAT Hand-Held Point-of-Care Analyzer for Dialysis Units
Authors: Gault M.H. , Harding C.E. , Duffett S. , Longerich L.
Published: April 2003

The i-STAT hand-held analyzer assays ten tests including electrolytes, gases, urea, glucose, ionized calcium, and hematocrit. Eight different cartridges assay one to eight tests. We have previously confirmed or demonstrated that accuracy and precision for blood assays are comparable to accepted laboratory methods. We now report similar results for hemodialysis dialysate and peritoneal dialysis effluent. The i-STAT analyzer is simple to use, and dialysis nurses produced accurate results with 20 min training. The results are viewed digitally on the analyzer and automatically on a small attachable printer. i-STAT blood analysis is most valuable when results are desired immediately, anywhere, including before, during and after dialysis in hemodialysis units. Hemodialysate analysis using i-STAT can be most valuable for rapidly checking dialysis machine function such as dialysate mixing and conductivity and ramping results and dialysate concentrations prepared in the unit. Peritoneal effluent analysis is useful for rapid evaluation of membrane function.
Significance of Leukocyte Infiltration in Membranous Nephropathy with Segmental Glomerulosclerosis
Authors: Saito Takao , Yusa Akira , Soma Jun , Ootaka Tetsuya , Sato Hiroshi , Ito Sadayoshi
Published: April 2003

Aim: To clarify the role of leukocyte subsets in the development of glomerulosclerosis (GS) and interstitial lesions which may contribute to the prognosis of membranous nephropathy (MN), we investigated infiltrating cells in both glomeruli and interstitium in biopsy specimens. Methods: Forty-one cases of MN were divided into two groups: MN with segmental GS (MN+GS; n = 21) and MN without GS (MN–GS; n = 20). There was no significant difference between both groups regarding clinical data at the time of the renal biopsy. The cells were analyzed with a three-layer indirect immunoperoxidase method using monoclonal antibodies against leukocyte common antigen, T cells, B cells, and monocytes/macrophages (Mo/Mφ). Results: Renal function tended to deteriorate during the final follow-up period in group MN+GS, but not in group MN–GS. The number of glomerular and interstitial leukocytes in group MN+GS were significantly higher than those in group MN–GS. Leukocytes were mostly Mo/Mφ in the glomerulus, while T cells and Mo/Mφ were predominant in the interstitium. In group MN+GS, there was a significant correlation in number of Mφ (CD68+) between glomeruli and interstitium, but not in group MN–GS. Conclusion: The results suggest that Mo/Mφ may play an important role in the development of segmental GS and interstitial lesions in MN which may be responsible for the incurability and poor prognosis.
The Advanced Glycation Endproduct, Pentosidine, in the Carpal Ligament in Patients with Carpal Tunnel Syndrome Undergoing Hemodialysis: Comparison with Idiopathic Carpal Tunnel Syndrome
Authors: Takahashi Masaaki , Hoshino Hironobu , Kushida Kazuhiro , Murata Hideyuki , Baba Satoshi , Inoue Tetsuo
Published: April 2003

Background/Aims: Carpal tunnel syndrome (CTS) is a major complication that occurs in the musculoskeletal system in patients on long-term hemodialysis (HD). Pentosidine is an advanced glycation endproduct (AGE) and there is evidence that shows AGEs contribute to the pathogenesis of the complications in patients undergoing HD. The aim of this study is to investigate whether pentosidine accumulates in the carpal ligament in patients undergoing HD with CTS in comparison with idiopathic CTS. Methods: Carpal ligaments and skin were obtained during surgery from 28 patients with CTS undergoing HD and 13 patients with idiopathic CTS (ID CTS). Pentosidine was measured by HPLC after hydrolysis of the samples, and amyloid deposits in the samples of HD CTS were examined histologically. Results: Pentosidine levels in ligament and skin were significantly higher in HD CTS than ID CTS. On the other hand, there was no difference in pyridinoline which is a physical cross-link between HD and ID CTS. Amyloid deposits were observed in 14 ligament samples, whereas there was none in 14 other samples. There was no significant difference in pentosidine and pyridinoline in ligament, pentosidine in skin, duration of HD and serum β2-microglobulin between the amyloid+ group and the amyloid– group. Conclusion: A greater concentration of pentosidine in the carpal ligament in HD patients compared with idiopathic patients suggests that an accumulation of AGEs contributes to one of the pathologies of occurrence of CTS in patients undergoing HD.
Sulfonylureas Stimulate Renin Secretion from the Perfused Kidney of the Rat
Authors: Ochi Hiroshi , Ikeda Tadasu
Published: April 2003

To elucidate whether sulfonylureas directly influence renin secretion, the effect of tolbutamide, glibenclamide, or chlorpropamide on renin secretion was investigated by using the perfused kidney of the rat. The isolated kidneys of male Wistar rats (200–250 g) were perfused with a medium containing 2 µM tolbutamide, 2 µM glibenclamide, and 2 µM chlorpropamide, respectively. Renin activity significantly increased from a basal value of 11.7 ± 3.6 to a peak value of 20.6 ± 5.5 ng/Ang I/ml/h with tolbutamide, from 14.4 ± 4.6 to 32.7 ± 6.5 ng/Ang I/ml/h with glibenclamide, and from 15.0 ± 4.9 to 30.4 ± 6.1 ng/Ang I/ml/h with chlorpropamide. The cAMP concentration in the effluent was not changed by the addition of the sulfonylureas. In kidneys perfused with a calcium-free medium, glibenclamide produced a significant increase in renin activity from a basal value of 13.4 ± 2.1 to a peak value of 30.6 ± 3.4 ng Ang I/ml/h. These results suggest that sulfonylureas stimulate renin secretion from perfused rat kidneys.
Erythropoietin Therapy in a Pregnant Post-Renal Transplant Patient
Authors: Shohaib Saad Al
Published: April 2003

Erythropoietin (EPO) is a glycoprotein hormone produced principally by the kidney and is the major stimulus for erythropoiesis. Recombinant human EPO has now been biosynthesized and is available for clinical use, particularly in patients with renal failure. EPO has been reported to be effective in treating anaemia due to chronic renal failure. It has been used in pregnancy to correct anaemia following renal transplantation with graft dysfunction. We report here the case of a post-renal transplant patient who became pregnant and developed severe anaemia which was not related to iron, B12, or folate deficiency. Her anaemia was successfully treated with EPO with no evidence of rejection or significant graft dysfunction following therapy. She tolerated EPO very well, and there was a successful outcome of the pregnancy. This case has encouraged us to conclude that EPO has a useful role in the treatment of anaemia in pregnant women following renal transplantation.
Does Captopril Have a Direct Pro-Apoptotic Effect?
Authors: Buemi Michele , Allegra Alessandro , Marino Demetrio , Marino Maria Teresa , Medici Maria Antonietta , De Pasquale Giuseppe , Ruello Antonella , Corica Francesco , Frisina Nicola
Published: April 2003

The beneficial effect of ACE inhibitors on cardiovascular remodelling from hypertension and ischemic disease may be due to the effect of these drugs on the proliferation/cell death balance. We therefore investigated the effect of the addition of captopril in vitro, on the onset of apoptosis in human vascular myocytes, by using a propidium iodide fluorescence analysis and a morphological analysis using the acridine orange technique. Captopril (0.23 mM) caused an increase in apoptotic phenomena that was more than 3.5-fold than in controls both at the 24th (7.7 vs. 2%) and the 48th h (10.1 vs. 3.8%). The addition of propranolol strengthened the effect on apoptosis. The induction of apoptotic phenomena may be a mechanism by which ACE inhibitors affect cardiovascular remodelling and it might also explain the favorable effect these drugs have on diseases such as IgA nephropathy and diabetic nephropathy.
Hemodialysis-Related Nodulocystic Acne Treated with Isotretinoin
Authors: Lin Ja-Liang , Shih I-Hsin , Yu Chun-Chen
Published: April 2003

Some hemodialysis patients, without taking any acnegenic agents, developed severe nodulocystic acne with unknown causes. Because nodulocystic acne poorly responds to conventional acne therapy and increases the black pigmentation in the face, it severely interferes with the quality of life of these patients. To investigate whether isotretinoin is effective in treating hemodialysis patients with severe nodulocystic acne, we undertook a prospective, randomized, single-blind study. A total of 20 patients with nodulocystic acne participated in the study, of whom 18 completed it. Ten patients received isotretinoin 10 mg/day (5 mg/capsule) for 3 months as a study group and the other 10 took placebo for 3 months as a control group. The severity of acne and treatment-related side effects were evaluated monthly by a questionnaire and laboratory evaluation which included liver function tests, blood lipids and blood platelet counts. The results showed isotretinoin treatment significantly reduced the severity of acne of the study group patients after 1 month (scales of acne severity: 4.0 ± 0.0 vs. 3.13 ± 0.35, p < 0.01) and 3 months (4.0 ± 0.0 vs. 1.5 ± 0.76, p < 0.01) of follow-up. In addition, the severity of acne of the study group patients was significantly less than that of the control group patients after 1 month (3.13 ± 0.35 vs. 3.80 ± 0.42, p < 0.01) and 3 months (1.5 ± 0.76 vs. 3.70 ± 0.48, p < 0.001) of treatment. Only mild side effects were noted. No significant changes of biochemical evaluation were found except that a mild elevation of aspartate aminotransferase was noted in the study group patients. However, two study group patients withdrew from the trial because of isotretinoin-related side effects and toxic hepatitis. In summary, our study first demonstrated that the small dose of isotretinoin effectively treated nodulocystic acne of hemodialysis patients and the side effects were mild. This result suggests that isotretinoin may be the treatment of choice for nodulocystic acne in end-stage renal disease patients with renal replacement therapy. The liver function and other isotretinoin-related side effects in these patients should be carefully monitored.
Effect of Ginsenoside-Rd in Cephaloridine-Induced Renal Disorder
Authors: Yokozawa Takako , Owada Shigeru
Published: April 2003

To determine whether ginsenoside-Rd ameliorates the renal injury induced by cephaloridine, the effect of cephaloridine was investigated in rats given ginsenoside-Rd preceding cephaloridine administration and in control rats given no ginsenoside-Rd. In control rats, blood, renal and urinary parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd was given orally for 30 consecutive days prior to cephaloridine injection, the activities of the antioxidation enzymes superoxide dismutase and catalase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. The urea nitrogen and creatinine levels in serum were decreased in rats given ginsenoside-Rd. Decreased urine volume, increased urinary osmotic pressure, and decreased urinary levels of glucose, protein, sodium and potassium demonstrated a protective action against the renal dysfunction caused by cephaloridine. In addition, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells exposed to cephaloridine.
Increased Urinary Excretion of Macrophage-Colony-Stimulating Factor (M-CSF) in Patients with IgA Nephropathy: Tonsil Stimulation Enhances Urinary M-CSF Excretion
Authors: Matsuda Mitsuhiro , Shikata Kenichi , Wada Jun , Yamaji Hiroaki , Shikata Yasushi , Doi Akira , Kosaka Michiya , Akagi Hirofumi , Masuda Yu , Ohmoto Yasukazu , Makino Hirofumi
Published: April 2003

Upper respiratory tract infection including chronic tonsillitis is considered to be involved in the onset and/or the progression of IgA nephropathy. It is well known that deterioration of urinary findings occurs after episodes of upper respiratory tract infection in patients with IgA nephropathy. We previously showed that the expression of macrophage-colony-stimulating factor (M-CSF) is increased in the glomeruli of patients with IgA nephropathy and correlated with glomerular mesangial proliferation, suggesting that M-CSF plays an important role in the progression of IgA nephropathy. In the present study, we measured the serum and urinary concentrations of M-CSF in patients with IgA nephropathy associated with chronic tonsillitis. Furthermore, we evaluated the effects of the local provocation test of tonsils (mechanical tonsil stimulation) on the serum and urinary concentrations of M-CSF in the following three groups: (1) IgA nephropathy with severe mesangial proliferation, (2) IgA nephropathy with mild mesangial proliferation, and (3) patients with chronic tonsillitis without renal disease. The serum and urinary levels of M-CSF in the groups with severe and mild IgA nephropathy were significantly higher than those in the chronic tonsillitis group. The urinary M-CSF level but not the serum M-CSF level was positively correlated with the degrees of mesangial proliferation and glomerular M-CSF expression in the renal biopsy specimens. The urinary M-CSF concentration was significantly increased after tonsillitis stimulation in both mild and severe IgA nephropathy groups. Enhanced urinary excretion of M-CSF prolonged for 7 days after tonsil stimulation in the severe IgA nephropathy group; in contrast, the urinay M-CSF level was increased for only 2 days after tonsil stimulation in the mild IgA nephropathy group. The urinary M-CSF level was not changed in the chronic tonsillitis group after tonsil stimulation. The serum concentrations of M-CSF were not changed after tonsil stimulation in these three groups. Our present results suggest that tonsil stimulation contributes to the progression of IgA nephropathy via enhancement of glomerular production of M-CSF. The urinary excretion of M-CSF may be a useful predictor to evaluate the relevance of chronic tonsillitis to the disease and the indication of tonsillectomy in patients with IgA nephropathy.
Plasma Glutathione Peroxidase Activity Is Reduced in Haemodialysis Patients
Authors: Roxborough Heather E. , Mercer Caroline , McMaster Dorothy , Maxwell A.Peter , Young Ian S.
Published: April 2003

Cardiovascular disease is the major cause of morbidity and mortality in patients with end-stage renal failure. Increased free radical production and antioxidant depletion may contribute to the greatly increased risk of atherosclerosis in these patients. Glutathione peroxidase (GPX) is an important antioxidant, the plasma form of which is synthesized mainly in the kidney (eGPX). The aim of this study was to assess the activity of eGPX in patients with end-stage renal failure on haemodialysis. Venous blood was collected from 87 haemodialysis patients immediately prior to and after dialysis and from 70 healthy controls. Serum eGPX activity was measured using hydrogen peroxide as substrate and immunoreactivity determined by ELISA. eGPX activity was significantly reduced in dialysis patients when compared to controls (106 ± 2.7 and 281 ± 3.6 U/l respectively, p < 0.001). Following haemodialysis, eGPX activity rose significantly to 146 ± 3.8 U/l, p < 0.001, although remaining below control values (p < 0.005). Immunoreactive eGPX, however, was similar in all groups (pre-dialysis 14.10 ± 1.26 µg/ml, post-dialysis 14.58 ± 1.35 µg/ml, controls 15.20 ± 1.62 µg/ml, p = NS). A decrease was observed in the specific activity of eGPX in patients when compared to controls (8.81 ± 1.14, 10.71 ± 1.54 and 21.97 ± 1.68 U/mg respectively, p < 0.0001). eGPX activity is impaired in patients undergoing haemodialysis and so may contribute to atherogenesis in renal failure.
Effect of Hyperosmolality upon the Mesothelial Monolayer Exposed in vivo and in situ to a Mannitol-Enriched Dialysis Solution
Authors: Gotloib Lazaro , Wajsbrot Valery , Shostak Avshalom , Kushnier Raisa
Published: April 2003

Studies done using the in vivo mouse model of population analysis of mesothelium showed that dialysis solutions containing high concentrations of glucose induced the development of a hypertrophic phenotype. Since these changes were neither related to the low pH nor to the presence of lactate buffer, we hypothesized that the presence of glucose was at the origin of the observed alterations. Theoretical analysis of the problem points to three possible mechanisms: hyperosmolality; metabolic changes derived from the high-glucose concentration itself, and/or the presence of products derived from the nonenzymatic degradation of glucose. The present study was designed to demonstrate or rule out the eventual effect of hyperosmolality upon the monolayer, applying the in vivo mouse model of population analysis of mesothelium. For this purpose, morphometric observations made in mice injected once a day during 30 consecutive days with a filter-sterilized 4.25% solution of mannitol (233.29 mM) were compared with those seen in intact mice and in a previously reported group of animals exposed to heat-sterilized fluid, having an equimolar concentration of glucose (235.9 mM), and the same osmolality (486 mosm/l) and electrolyte concentrations. The main findings observed in the mannitol-treated mice during the period of exposure included increased cell size and cytoplasmic surface area, as well as decreased cell viability. The regenerative capabilities of the exposed mesothelium remained intact. After a recovery period of 7 days, the aforementioned parameters reverted to normal values. This pattern is significantly different from the hypertrophic, senescent and low regenerative phenotype observed in mice treated with the high-glucose concentration solution. We conclude that, at least in the in vivo and in situ setup, the detrimental effects of hyperosmolality alone upon the exposed mesothelium are quite limited and fully reversible within a recovery period of 7 days.
Differential Distribution of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Proteins in Experimental Diabetic Rat Kidney
Authors: Miyatake Nobuyuki , Shikata Kenichi , Wada Jun , Sugimoto Hikaru , Takahashi Shin-Ichiro , Makino Hirofumi
Published: April 2003

Insulin-like growth factor-1 (IGF-1) is a peptide growth factor, and its activity is modulated by interaction with the family of IGF binding proteins (IGFBP-1 to 6). IGF-1 is detected in rat kidney and has metabolic and growth effects. To explore the possible involvement of IGFBPs in glomerular hypertrophy in streptozotocin (STZ)-induced diabetic rat, the immunolocalization of IGF-1 and IGFBPs were investigated. IGF-1 was gradually increased in the glomeruli of diabetic rats and correlated with glomerular hypertrophy. IGFBP-1 was transiently increased at 1 week after the STZ injection and declined to control level during the following period. In contrast, IGFBP-4 was increased in the diabetic glomeruli throughout the observation period. With insulin treatment, the levels of IGF-1, IGFBP-1 and 4 were normalized and glomerular hypertrophy was prevented. Initial glomerular hypertrophy of diabetic nephropathy is a related IGF-1 action, which may be modulated by IGFBP-1 and 4.
Effect of the Platelet-Derived Growth Factor Antagonist Trapidil on Mesangial Cell Proliferation in Rats
Authors: Futamura Akihiro , Izumino Kiyoshi , Nakagawa Yuko , Takata Masanobu , Inoue Hiroshi , Iida Hiroyuki
Published: April 2003

Platelet-derived growth factor (PDGF) is known as a potent mediator in the proliferation of mesangial cells in culture and in mesangial proliferative nephritis. The present study was undertaken to evaluate the effect of trapidil, an antagonist of PDGF, on mesangial cell proliferation in culture and in anti-Thy-1.1 nephritis in rats. Trapidil significantly inhibited 3H-thymidine incorporation in the mesangial cells stimulated by PDGF BB and suppressed mesangial cell proliferation in culture in a dose-dependent manner. In anti-Thy-1.1 nephritis, a significant reduction in the number of total glomerular cells and also proliferating (proliferating cell nuclear antigen positive) cells was demonstrated on day 7 in the rats treated with trapidil as compared with controls. Although renal function expressed as blood urea nitrogen and creatinine levels did not differ between rats with and without trapidil treatment, the present results suggest a salutary effect of trapidil on mesangial cell proliferation. PDGF, therefore, could play an important role in mediating mesangial cell proliferation.
Cerebral Salt-Wasting Syndrome: Does It Exist?
Authors: Maesaka John K. , Gupta Sandeep , Fishbane Steven
Published: April 2003

Cerebral salt-wasting syndrome (CSWS) has been regarded as a misnomer of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We take the position that CSWS does exist and might be more common than SIADH. Differentiation between groups has been difficult because of overlapping signs, symptoms, and associated diseases. Euvolemia in SIADH and hypovolemia in CSWS may be the only contrasting variables. However, clinical assessment of extracellular volume is accurate in about 50% of these patients. Determination of serum urate and fractional excretion rates of urate can differentiate one group from the other. In both groups, hyponatremia coexists with hypouricemia and increased fractional excretion of urate. When the hyponatremia is corrected by water restriction, hypouricemia and elevated FEurate correct in SIADH but persist in CSWS. Persistent hypouricemia and elevated FEurate were commonly noted with pulmonary and/or intracranial diseases. The absence of intracranial diseases in some patients suggests that renal salt wasting might be a more appropriate term than CSWS. A review of renal/CSWS reveals three studies involving hyponatremic neurosurgical patients who had decreased blood volume, decreased central venous pressure, and inappropriately high urinary sodium concentrations in the majority of them, suggesting that CSWS was more common than SIADH in neurosurgical patients. Evidence for the presence of a plasma natriuretic factor in CSWS is presented.
Cerebral Salt-Wasting Syndrome
Authors: Oh Man S. , Carroll Hugh J.
Published: April 2003

It is widely believed that the cerebral salt-wasting syndrome (CSWS) exists as an entity distinct from the syndrome of inappropriate ADH secretion, and that it is characterized by evidence of severe renal salt wasting that results in volume depletion and hyponatremia. Proof of the existence of CSWS as an entity requires documentation of renal salt wasting and volume depletion. The present review has been undertaken to examine the evidence that the CSWS is a separate entity. In this effort, we have discussed various methods of documentation of volume depletion, and then reviewed reported cases of CSWS to determine whether volume depletion and renal salt wasting have been clearly demonstrated. Our review has led us to conclude that not one case of purported CSWS has demonstrated clear evidence of volume depletion and renal salt wasting. If renal salt wasting had been proven in these cases, we would conclude that the likely site of renal salt transport was the proximal tubule. The proximal site of salt transport defect has been suggested by the absence of hyperreninemia and hypokalemia, which would be a distinguishing feature of Bartter’s syndrome and Gitelman’s syndrome.
Effect of Vitamin E on Adriamycin- Induced Nephrotoxicity at the Ultrastructural Level in Guinea Pigs
Authors: Görgün M. , Erdogan D. , Abban G. , Türközkan N. , Elbeg Ş.
Published: April 2003

It is known that Adriamycin, which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in several organs. In this study, we have established that vitamin E has some beneficial effects on the kidney by protecting it from some of the toxcity induced by Adriamycin. A study was carried out which comprised one control group and two experimental groups of guinea pigs. In the experiment Adriamycin was administered either alone (group II) or together with vitamin E (group III). The results of groups II and III were compared with controls (group I). The kidneys were subsequently removed and examined by routine electron microscopic techniques. We found that vitamin E administered together with Adriamycin could reverse some of the degenerative changes caused by Adriamycin.
High Glucose Induces a Hypertrophic, Senescent Mesothelial Cell Phenotype after Long in vivo Exposure
Authors: Gotloib Lazaro , Shostak Avshalom , Wajsbrot Valery , Kushnier Raisa
Published: April 2003

Previous studies, done using our mouse model for population analysis of the mesothelium, showed evidence indicating that in vivo, long-term exposure (up to 30 days) of the peritoneum to high-glucose (4.25% D-glucose) concentration dialysis solutions resulted in a hypertrophic mesothelial phenotype characterized by increased cell surface area, multinucleation, low proliferative capabilities, reduced cell viability, and enhanced enzymatic activity. These elements that define a senescent population of cells were not related to the pH of the fluid and its osmolality, or to the presence of buffer lactate. The present study was designed to explore the adverse effects of a lactate-free, filter-sterilized, high-D-glucose concentration solution (4.25%) at normal pH and prepared in Hanks’ buffered salt solution after 2 h, 15 and 30 days of once a day intraperitoneal injection. Analysis of our observations indicate that in vivo exposure of the mesothelium to a high-glucose concentration induced a decreased density of the cell population, made up by larger and multinucleated cells, the viability of which was significantly lower than that observed in intact unexposed mice. The prevalence of mitosis showed an early and short-lived acceleration (up to 3 days), followed by values near zero during the rest of the follow-up period. So far, the main effect of the high-glucose concentration appears to result not from a mechanism of cytotoxicity, but from a substantial change in the life cycle of the exposed cell population, leading to their premature senescence and death in apoptosis. We hypothesize that this outcome may well be mediated by sustained oxidative stress derived from both a reduced production of scavengers, as well as the increased generation of oxygen-reactive species.
Hemodialysis Neutropenia Correlates with a Decreased Filterability and an Increase in the Number of Cytoplasmic Actin Filaments in Peripheral Blood Neutrophils, Which Is Preceded by a Decrease in the Number of Surface Expression of L-Selectin
Authors: Iijima Shigeruko , Otsuka Fujio , Hasegawa Yuichi , Koyama Akio
Published: April 2003

In order to clarify the precise cellular mechanism of hemodialysis neutropenia, we examined the changes in the viscoelasticity of peripheral blood neutrophils using both the micropore and the microchannel filtration methods, and the changes in the neutrophil surface expression of Mac-1, L-selectin and sialyl Lewis X and the cytoplasmic expression of the actin filaments using a flow cytometric analysis during a dialysis session. Five patients with chronic renal failure were selected who showed a nadir leukocyte count in peripheral blood at 30 min after the initiation of the dialysis session. The neutrophil count also reached a nadir at 30 min and thereafter returned to almost the predialysis level by 180 min. Both the micropore filtration time and the microchannel passage time, which reflect the viscoelasticity of the peripheral blood neutrophils, correlated inversely with the neutrophil count. At the nadir of neutropenia, the neutrophils were observed to have become both adhesive and viscoelastic. The actin filaments in the neutrophil cytoplasm gradually increased in number from the start of dialysis, reaching a peak level at 30 min, and thereafter decreasing to predialysis levels. The Mac-1 expression continuously increased up from 30 min until the end of dialysis. The L-selectin expression first decreased at 15 min, but thereafter returned to predialysis levels within 60 min. The SLex expression did not change throughout the course of the session. These results thus indicated the neutrophil counts during a dialysis session to inversely correlate with the viscoelasticity of the neutrophils expressed by the micropore filtration time or microchannel passage time, which possibly depends on the contents of cytoplasmic actin filaments. In addition, the shedding of L-selectin from neutrophil surface may also be involved in the first step of hemodialysis neutropenia.
Volatile Alkanes and Increased Concentrations of Isoprene in Exhaled Air during Hemodialysis
Authors: Capodicasa Enrico , Trovarelli Gianfranco , De Medio Gianna Evelina , Pelli Maria Antonietta , Lippi Giorgio , Verdura Claudio , Timio Mario
Published: April 2003

In this study we examined breath volatile hydrocarbon concentrations in exhaled air of hemodialysis patients. We assessed both C2–C5 alkanes – among them ethane and pentane the production of which in man is essentially due to the action free radicals exert on polyunsaturated fatty acids – and isoprene, an unsaturated hydrocarbon the biosynthesis and biological effects of which are the subject of controversy and mounting interest. Twenty patients were studied. Evaluation was performed intrapatient in the breath of patients with chronic renal failure, before and after dialysis (20 patients) and, in the same cases, during hemodialytic treatment (10 patients). Breath concentrations of these volatile hydrocarbons, determined before dialysis, were not different from those of normal subjects. Dialysis did not modify the levels of the C2–C5 saturated hydrocarbons ethane, propane, butane and pentane. Instead, there was a marked increase in isoprene in all patients (basal values rose by a mean of 270%). Since isoprene was not present in the fluids or filters used for dialysis and there were only traces in the ambient air, the isoprene must have been produced endogenously during hemodialysis. As no situation has previously been reported to increase endogenous production of isoprene in humans, patients in hemodialysis offer a unique opportunity to investigate in depth the medical, biological and toxicological aspects of isoprene.