bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Lower Infundibulopelvic Angle, Lower Infundibulum Diameter and Inferior Calyceal Length on Stone Formation
Authors: Gökalp Adil , Tahmaz Lütfi , Peskircioglu Levent , Özgök Yaşar , Saglam Mutlu , Kibar Yusuf , Harmankaya A. Çetin
Published: April 2003

The effect of anatomical factors such as lower infundibulopelvic angle (LIPA), lower infundibulum diameter (LID) and inferior calyceal length (ICL) on renal stone formation was investigated. These parameters were measured from noncalculous kidneys of 40 healthy kidney donors. The same parameters from 119 patients with single, unilateral, nonobstructive lower calyceal stone were also measured. LID and ICL were significantly higher in calculous kidneys when compared to the control group. On the other hand, the difference between the LIPA of the two groups was not significant. It is concluded that LID and ICL could be good indices in determining lower calyceal stone formation.
A Phase II Trial of Gallium Nitrate in Patients with Androgen-Metastatic Prostate Cancer
Authors: Senderowicz Adrian M. , Reid Robert , Headlee Donna , Abornathy Troy , Horti József , Lush Richard M. , Reed Eddie , Figg William D. , Sausville Edward A.
Published: April 2003

Introduction: Due to in vitro data suggesting antitumor activity with gallium nitrate, we sought to evaluate the safety and activity in patients with androgen-independent prostate cancer. Method: Patients were eligible for this study if they had an ECOG performance status of ≤2, stage D2 metastatic prostate cancer that was progressing following combined androgen ablation (medical or surgical castration plus antiandrogen) and had failed antiandrogen withdrawal. Therapy consisted of gallium nitrate (200 mg/m2/day) as a continuous infusion for 7 days, administered every 21 days, with hydration (100 ml/m2/h). Individuals that had previously received suramin were treated at a dose of 150 mg/m2/day of gallium nitrate. Results: Eight patients were enrolled: 4 patients at the 200 mg/m2/day dose level and 4 patients at the lower dosage (150 mg/m2/day). One of 8 patients had a >75% decline in prostate-specific antigen (PSA), 3 patients had stable PSA values for 17, 18 and 22 weeks, and 4 patients had progression by PSA (>50% increase over baseline). Anemia requiring transfusion occurred in 5 of 8 patients (63%). Two patients (25%) developed grade 4 toxicity: 1 patient developed complete blindness with partial reversal over 12 months, and another patient had pulmonary infiltrates, hypoxemia, and fever. Serious adverse events were not correlated to prior suramin exposure, or gallium plasma concentrations (total or free), but appeared to be related to cumulative cycles of gallium nitrate. Remaining adverse events were grade 1 or 2. No patients developed renal or neurological toxicity. Conclusion: This trial was prematurely terminated because repeated administration of gallium nitrate was poorly tolerated in an elderly population with androgen-independent prostate cancer. Gallium had modest clinical activity in this disease.
Single Ectopic Vaginal Ureter Diagnosed by Computed Tomography
Authors: Komatsu Kazuto , Niikura Susumu , Maeda Yuji , Ishiura Yoshiyuki , Yokoyama Osamu , Namiki Mikio
Published: April 2003

A case of a single ectopic vaginal ureter in a 6-year-old girl with urinary incontinence is reported. Excretory urography and renal sonography failed to visualize the dysplastic kidney, but enhanced computed tomography clearly demonstrated a poorly functioning hypoplastic kidney, ectopic ureter and vagina filled with contrast medium.
Pyelic Metastasis from a Renal Cell Carcinoma following Partial Nephrectomy
Authors: Da Silva Eloisio Alexsandro , Telo Eduardo Zungri , Pampin Francisco Neira , Sacristan Felipe , Buceta Ana de la Fuente
Published: April 2003

The majority of ureteropelvic metastatic tumors are of non-urologic origin. A case of metastatic clear cell adenocarcinoma to the renal pelvis in a patient with a bilateral, asynchronous renal tumor is presented. Conservative surgical treatment involved open pyelotomy and local resection of the tumor. At the 12-month follow-up, the patient is alive, asymptomatic and not on dialysis. The hypothesis for the mechanisms of dissemination and the relevance of conservative treatment are discussed.
Extracorporeal Shock Wave Lithotripsy Monotherapy of ‘Stoned’ Internal Ureteral Stent in Children
Authors: Slavković A. , Vlajković M. , Širić Z. , Stefanović V.
Published: April 2003

A case of ESWL treatment, as monotherapy, of a ‘stoned’ ureteral stent in a 12-year-old boy was described. Two years previously, the patient had pyelolithotomy with staghorn stone removal, and double-J stent was left indwelling intraoperatively. The patient was lost for follow-up for 2 years, when he had multiple stone formation adherent to the whole length of the stent. Four ESWL sessions were required before the stent was freed for removal.
Focal Xanthogranulomatous Pyelonephritis with AssociatedBone Metaplasia
Authors: Selli C. , De Antoni P. , Moro U. , Crisci A. , Bartoletti R. , Scott C.A.
Published: April 2003

Focal xanthogranulomatous pyelonephritis of the left lower pole was accidentally discovered in a 34-year-old woman at sonography. The patient had no history of stones and urinary tract infection and both conventional radiology and CT scan revealed radiated calcifications within a well-circumscribed mass. Surgical treatment consisted of enucleoresection of the lesion, and histopathology revealed a nucleus of bone metaplasia. To the best of our knowledge, metaplastic bone formation has never been documented before with xanthogranulomatous pyelonephritis.
Leiomyoma of the Ureter
Authors: Yashi Masahiro , Hashimoto Shinichi , Muraishi Osamu , Tozuka Kazuhiko , Tokue Akihiko
Published: April 2003

We report a case of leiomyoma of the ureter, and the patient underwent partial ureteral resection. This is the 8th case reported after 1955, and the clinical features of ureteral leiomyomas of these 8 cases are discussed.
Incidental Prostate Cancer: The Importance of Complete Prostatic Removal at Cystoprostatectomy for Bladder Cancer
Authors: Abbas Farhat , Biyabani Syed Raziuddin , Pervez Shahid
Published: April 2003

Patients with invasive bladder cancer could be at a higher risk for a second malignancy such as an unsuspec- ted prostate cancer. We report a case of muscle-invasive transitional cell carcinoma of the urinary bladder with incidental adenocarcinoma of prostate, and review the literature to highlight the importance of complete prostatic removal to prevent residual disease.
Ulcer Perforation in Gastric Urinary Conduit: Never Use a Gastric Segment in the Urinary Tract if There Are Other Options Available
Authors: Tainio Hanna , Kylmälä Timo , Tammela Teuvo L.J.
Published: April 2003

A male patient, who had had a conservatively treated hemorrhagic peptic ulcer 12 years earlier, underwent gastrocystoplasty after radical cystoprostatectomy for carcinoma of the urinary bladder. After operation the patient suffered urinary incontinence and dysuria which he found so bothersome that the gastric bladder was converted to diversion using the same gastric segment as a tube. Postoperatively there were clots of blood in stomal urine and after the kidneys had been drained intestinal fluid oozed from the stoma. On the 14th postoperative day the patient died of pulmonary embolism. The autopsy showed a perforated peptic ulcer in the gastric segment resulting in a closed fistula to the small bowel. Most probably the reason for development of the peptic ulcer was stress caused by the operation and it might have been avoided by using hydrogen-blocking agents. This case seriously questions whether a gastric segment should be used in the urinary tract at all, and at least it should never be used as a conduit.
Unusual Calcification of the Right Kidney
Authors: Gygi Christian M. , Meuwly Jean-Yves , Leisinger Hans-Jörg
Published: April 2003

For economic reasons, the tendency in western communities is to simplify the investigations for a given pathology. This case is typically the one where some more money has to be invested to achieve the correct diagnosis.
Cystic Lymphangioma of Retroperitoneum and Groin
Authors: Yasui Takahiro , Akita Hidetoshi , Sasaki Shoichi , Ueda Kousuke , Kobayashi Katsumasa , Kohri Kenjiro
Published: April 2003

We report a case of cystic lymphangioma of the retroperitoneum and groin. A 38-year-old male was referred to our hospital due to a right inguinal mass without tenderness. CT, MRI revealed retroperitoneal mass and inguinal mass. Biopsy of the inguinal mass was performed. The lesion was multicystic, and adherent to the surrounding tissue. Pathological examination revealed lymphangioma.
A Germline Homozygote Deletion of the Glutathione-S-Transferase Mu1 Gene Predisposes to Bladder Cancer
Authors: Mungan N. Aydin , Aben Katja K.H. , Beeks Esther , Kampman Ellen , Bunschoten Annelies , Bussemakers Marion , Witjes J. Alfred , Kiemeney Lambertus A.L.M.
Published: April 2003

Introduction and Objectives: Numerous studies have shown smoking and specific occupational exposures to be risk factors for bladder cancer. The risk of bladder cancer may be modified by the activity of carcinogen metabolizing enzymes. The glutathione-S-transferase Mu1 enzyme (GSTM1) detoxifies arylepoxides which are formed after exposure to certain polycyclic aromatic hydrocarbons and possibly aromatic amines. Approximately 40% of Caucasians lack GSTM1 activity due to a homozygous deletion of the GSTM1 locus on chromosome 1p13 (GSTM1 0/0 genotype). The aim of this study was to evaluate the combined effect of smoking and GSTM1 genotype on the risk of bladder cancer. Materials and Methods: Sixty-one patients with transitional cell carcinoma of the bladder and 69 controls matched for age and sex were enrolled from the outpatient clinic. Lifestyle information was collected with a standardized questionnaire. DNA was extracted from white blood cells. The GSTM1 genotype was determined by a PCR-based method. Results: 92% of the 61 patients had a history of smoking compared with 81% of the controls. There was a significant dose-response relationship for pack-years of smoking (trend test: p = 0.003). The proportion of GSTM1 0/0 genotype among patients was 62% compared with 43% among controls (odds ratio = 2.1; 95% CI 1.1–4.3). The expected interaction between smoking and GSTM1 genotype was not observed. Conclusions: This study confirms the findings that a germline homozygous deletion of the GSTM1 gene predisposes to bladder cancer. An interaction with smoking was not found.
No Change with Age in Semen Volume, Sperm Count and Sperm Motility in Individual Men Consulting an Infertility Clinic
Authors: Krause Walter , Habermann Barbara
Published: April 2003

In the human male, Leydig cell function of the testis declines slowly but significantly with age. A similar decline in the spermatogenic activity, however, is not well proven by consistent data. Cross-section studies quoted in the literature mostly describe only minor changes in different sperm parameters with age. In our database we identified 253 men who had attended our department since 1989 for subsequent semen analyses at intervals of more than 1 year. The semen analyses were performed according to the guidelines of the WHO with the exception that motility parameters were measured by CASA. The mean interval between the two analyses was 967 days with a range of 341–2,731 days. None of the parameters evaluated showed a significant increase or decrease with time. The mean seminal volume was identical in the two analyses. Mean sperm count increased during the observation period by 12 · 106 spermatozoa/year. In 177 patients an increase and in 73 patients a decrease occurred. Also a corresponding increase in total sperm count was observed. Sperm motility increased in 123 patients, and it decreased in 123 patients. Only slight differences in the increase or decrease of the two parameters between the groups of patients with and without a history of genital diseases and/or varicocele were found. The results of our study do not support the suggestion that the sperm parameters decrease with age.
Identification of the Origin of a Vesical Mass Occurring after Cadaveric Renal Transplantation Using Short TandemRepeat Marke rs
Authors: Yamamoto Naoki , Nagai Atsushi , Kuriyama Manabu , Ishihara Satoshi , Ohya Isao , Deguchi Takashi
Published: April 2003

We report a case of polypoid cystitis in a 54-year-old female occurring 4 years after cadaveric kidney transplantation. Endoscopic exploration revealed a polypoid tumor near the stoma opened for the transplanted ureter. The diagnosis of polypoid cystitis was confirmed histopathologically. Genotyping of cells from the tumor with polymorphic short tandem repeat (STR) and amelogenin loci revealed that the tumor contained alleles from both the donor and recipient. Molecular genetic analysis provided strong evidence that the tumor cells arose from the donor tissue.
Localized Fibrosis of the Corpus cavernosum: An Example of Fibrosis Arising from the Vascular Smooth Muscle Cells
Authors: Lopes Maria , Lanzafame Salvatore , Magro Gaetano
Published: April 2003

We report a rare case of a localized fibrosis of the corpus cavernosum (CC) presenting as a nodular mass in the dorsal region of the penis without abnormal curvature of the organ. Histological and immunohistochemical examination revealed a fibrotic process, involving CC but not tunica albuginea, arising from the smooth muscle cells of the vascular channels. Two different morphological phases were identified in these vascular lesions: proliferative and residual phase. The proliferative phase was characterized by hyperplasia and moderate fibrous thickness of the smooth muscle layer of the vascular channels of CC, resulting with the formation of concentric perivascular cuffs and nodules. The residual phase was characterized by a progressive nodular fibrotic transformation with narrowing of the original vascular channels and replacement of the normal CC structures. The cells of this phase exhibited an immunophenotype of both fibroblasts (vimentin+; α-smooth muscle actin–) and myofibroblasts (vimentin+; α-smooth muscle actin+). The clinicopathological features of the lesion and histogenetic considerations are discussed.
Massive Hematuria in Adults with Klippel-Trenaunay Syndrome Associated with Vascular Malformation of the Bladder
Authors: Shekarriz Bijan , Upadhyay Jyoti , Smith Craig , Kazmers Andris , Frontera Rene
Published: April 2003

Although hematuria has been reported in children with Klippel-Trenaunay syndrome, it is a rare presentation in the adult population. Two cases of massive hematuria in adults with Klippel-Trenaunay syndrome are reported here. A unique feature was venous malformations of the bladder which were responsible for massive recurrent bleeding in 1 patient. The clinical presentation and management are discussed. Conservative endoscopic and arteriographic control seems to be appropriate as initial management in these patients.
Increased Sensitivity of Myeloid Leukemia Cell Lines: Potential of Lovastatin as Bone-Marrow-Purging Agent
Authors: Scheffold Christian , Schöttker Björn , Lefterova Petja , Csipai Markus , Glasmacher Axel , Huhn Dieter , Neubauer Andreas , Schmidt-Wolf Ingo G.H.
Published: April 2003

Lovastatin reduces the isoprenylation of p21ras via suppression of mevalonic acid generation. Lovastatin has been shown to reduce tumor cell proliferation in a dose-dependent manner. Here, the potential of lovastatin for purging leukemia cells from bone marrow was investigated using the myeloblastic cell lines K562 and KG-1 as a model system, derived from an erythroleukemia and an acute myelogenous leukemia, respectively. Optimal purging conditions were determined using an MTT proliferation and a leukemia colony assay. Elimination of leukemia cells was time- and dose-dependent. Depletion of K562 was 2.5 logs for 100 μM of lovastatin at 72 h of incubation. Compared to another purging agent, 100 μg/ml mafosfamide had an activity comparable to 100 mM lovastatin. Interestingly, KG-1 acute myelogenous leukemia cells were even more sensitive to lovastatin than K562 cells. In clonogenic assays, 100 μM of lovastatin resulted in a 3- to 4-log reduction of K562 colonies. Lovastatin had a progressive effect on normal hematopoietic progenitor cells. At a concentration of 100 μM of lovastatin, CFU-GM colonies were reduced by 1–2 logs. In conclusion, a differential effect on leukemia and normal progenitor cells could be detected in a clonogenic assay. These results suggest that lovastatin deserves further study as an agent for ex vivo marrow purging.
Factors Influencing Effectiveness of Deferiprone in a Thalassaemia major Clinical Setting
Authors: Del Vecchio Giovanni Carlo , Crollo Elisabetta , Schettini Federico , Schettini Francesco , Fischer Roland , De Mattia Domenico
Published: April 2003

The effectiveness of deferiprone (L1) and the influence of other factors were determined in a clinical setting. Patients of Southern Italian origin, affected by β-thalassaemia major (n = 13: 7 M, 6 F), aged 10–28 years (median 18 years), were treated with L1 within a ‘Controlled Programme’ of the Italian Ministry of Health. Desferrioxamine could not be administered in these patients because of anaphylactic reactions or other serious side effects. L1 was considered to be effective when the liver iron concentration was reduced or stable as measured by biomagnetic liver susceptometry. L1 proved to be effective in 3 out the 9 evaluable patients. A high pre-L1 iron overload was the main clinical factor influencing L1 effectiveness.
Granulocyte-Macrophage Colony-Forming-Unit Assay and Liquid Suspension Culture of Bone Marrow and Peripheral Blood in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia
Authors: Liang Der-Cherng , Chen Shu-Huey , Liu Hsi-Che , Yu Shu-Fang , Kuo Mei-Chuang
Published: April 2003

Granulocyte-macrophage colony-forming-unit (CFU-GM)-assays and/or liquid suspension cultures of bone marrow (BM) and peripheral blood (PB), using human placental conditioned medium as a source of colony-stimulating activity, were performed in 125 children with newly diagnosed acute lymphoblastic leukemia (ALL). Unlike the previous small series which invariably showed poor BM granulocyte-macrophage colony and cluster formations, we found 3 growth patterns. A poor-growth pattern was seen in 101 patients. A low-growth pattern with BM colony and cluster formations in the lower range of the normal limits was observed in 6 patients. All 6 patients had low-risk ALL, and the in vitro growth may reflect the residual normal CFU-GM in BM. Thirdly an over-growth pattern was noted in one patient with refractory ALL. In 49 cases where liquid suspension cultures of BM were performed, 4 had a normal-growth pattern and 42 had apoptotic cells and/or few residual granulocytic/monocytic cells after 7 days of culture. However, in both B cell ALL cases and in 1 refractory T cell ALL case with hyperleukocytosis, repetitive liquid suspension cultures of BM and PB consistently revealed an extensive growth of lymphoblasts. Thus, an over-growth pattern in either the BM CFU-GM assay or liquid suspension culture of BM or PB in children with ALL at diagnosis may indicate a refractory or aggressive disease. A low-growth pattern in the BM CFU-GM assay in children with ALL at diagnosis probably predicts a favorable outcome.
A Patient with Congenital Dyserythropoietic Anaemia Type III Presenting with Stillbirths
Authors: Jijina F. , Ghosh K. , Yavagal D. , Pathare A.V. , Mohanty D.
Published: April 2003

A 28-year-old female patient presented with recurrent stillbirths between 28 and 30 weeks of gestation. At least one of the stillborn was hydropic at birth; α-thalassaemia and Rh isoimmunisation were ruled out. The patient was found to be suffering from congenital dyserythropoietic anaemia (CDA) type III, a rare form of congenital anaemia inherited as an autosomal dominant character in some families. It is tempting to speculate that at least the hydropic stillborn inherited the same disorder from the mother. CDA type III as a cause of hydrops fetalis has not been reported in the literature. The patient, who was transfusion-dependent, underwent splenectomy. Subsequently she did not need any transfusion for the last 6 months.
Hyposplenism from Mycobacterium avium Complex Infection in a Patient with AIDS and Immune Thrombocytopenia
Authors: Khan Amir M. , Harrington Robert D. , Nadel Martin , Greenberg Bernard R.
Published: April 2003

We describe a patient with HIV-related immune thrombocytopenic purpura with known Mycobacterium avium complex (MAC) infection presenting with intracerebral hemorrhage associated with severe thrombocytopenia who failed splenectomy following unsuccessful trials of corticosteroids and intravenous immunoglobulin. His presplenectomy peripheral blood smear showed Howell-Jolly bodies and microscopic examination of his spleen demonstrated multiple granulomas with numerous acid-fast organisms replacing the normal splenic tissue. We postulate that splenic hypofunction secondary to overwhelming MAC infection contributed to the failure of the thrombocytopenia to promptly respond to splenectomy.
Donor Leukocyte Infusions for Acute Myeloid Leukemia Relapsing after Stem Cell Transplantation
Authors: Soysal Teoman , Başlar Zafer , Ferhanoglu Burhan , Akman Nuran
Published: April 2003

Relapse after stem cell transplantation (SCT) remains one of the major causes of mortality in leukemia. In an analysis including a large number of patients by the Seattle team, it was found to be 21% in acute myeloid leukemia (AML) [1]. The stage of the disease before transplantation, T cell depletion of the stem cell source, absence of graft-versus-host disease (GVHD), a syngeneic donor and type of the conditioning regimen seem to be important predictors of relapse after SCT [1, 2]. The time to relapse after SCT has been found to be the most important prognostic factor; relapses within the first 100 days after transplantation had the worst prognosis, while the best results were obtained in patients relapsing after the first year [1].
Use of Desmopressin for Prophylaxis of Surgical Bleeding in Factor XI-Deficient Patients
Authors: Bauduer Frédéric , Bendriss Philippe , Freyburger Geneviève , Ducout Louis , Marti Bernard
Published: April 2003

Desmopressin represents a well-established treatment for patients with von Willebrand disease and mild hemophilia A [1, 2]. Recently, this drug has been used with success in two symptomatic factor XI (FXI)-deficient individuals before surgery [3]. We report herein our own experience with 2 patients.
Angioimmunoblastic Lymphadenopathy with Dysproteinemia: Emphasis on Pathogenesis and Treatment
Authors: Sallah Sabah , Gagnon Gregory A.
Published: April 2003

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever, hepatosplenomegaly, hemolytic anemia, and polyclonal hypergammaglobulinemia. Morphologically, the involved lymph nodes demonstrate complete effacement of the normal architecture, prominent neovascularization and infiltration by immunoblasts and plasma cells. Other terms that have been used to describe this entity include diffuse plasmacytic sarcomatosis, immunoblastic lymphadenopathy, lymphogranulomatosis X, and immunologic aberrations in idiopathic reticulosis. Initially, AILD was thought to be a disease of B-cell origin that represented reactive immune response to unknown stimulus and high potential for malignant transformation. It is now evident that AILD in 80% of cases follows an aggressive course with short median survival, especially, if complete response with chemotherapy is not achieved. Immunologic and molecular studies have demonstrated that the majority of AILD cases are T-cell clonal disorders. Despite the numerous reports on the role of Epstein-Barr virus in this disorder, it is unknown whether the presence of this virus is associated with the immune defect that accompanies AILD, or whether it is a pathogenetic factor. In contrast to non-Hodgkin’s lymphomas, a stage is not usually assigned to the patient since the disease is systemic in nature, subsequently, parameters such as extent of disease and tumor bulk used to identify high-risk patients with non-Hodgkin’s lymphomas, do not appear to correlate with disease activity or prognosis in AILD. Treatment of AILD has been unsatisfactory, with approximately 25% of patients achieving complete and sustained remission when combined chemotherapy agents are used. This article is devoted to a discussion of the different manifestations, suggested pathogenesis, and treatment of AILD.
Comparison of Progenitor Cell Content in Sequential Peripheral Blood Progenitor Collections after Mobilization with Chemotherapy and Granulocyte Macrophage Colony- Stimulating Factor
Authors: Chang Eric , Parker John , Groshen Susan , Watkins Kristy , Douer Dan
Published: April 2003

Optimal timing of peripheral blood progenitor cell (PBPC) harvest to collect maximal stem cell numbers is unknown. We assessed the progenitor cell content in 128 PBPC harvests from 21 patients primed with chemotherapy and granulocyte macrophage-colony stimulating factor (GM-CSF) in relation to absolute neutrophil count (ANC) at collection time. Samples were obtained by leukapheresis during rebound from chemotherapy-induced neutropenia while receiving GM-CSF, and assayed by flow cytometry for CD34+ and by colony assays for CFU-GM and BFU-E. The CD34+ cell concentrations per sample tended to be greater at an ANC <1,000 mm3 and decreased with rising ANC (p = 0.001). The CFU-GM and BFU-E concentrations per sample remained relatively constant with rising ANC (p = 0.72, p = 0.90, respectively). Total CD34+ cell number per harvest per kg slightly increased with ANC levels (p = 0.044) whereas the total CFU-GM and the total BFU-E per kilogram increased more modestly with rising ANC (p < 0.001, p < 0.001, respectively). We conclude that after priming with chemotherapy and GM-CSF, PBPC could be collected at different absolute neutrophil counts without greatly affecting total CD34+ cell numbers. The greater concentration of CD34+ progenitor cells at a lower ANC together with the CFU-GM and BFU-E peaking with higher ANC suggest a less mature progenitor cell population at lower ANC levels.
Safety Screening of Drugs in Cancer Therapy
Authors: Nath J. , Krishna G.
Published: April 2003

Development of new drugs requires a thorough investigation of efficacy and safety of pharmaceuticals. The potential risks and benefits of drugs used in chemotherapy are carefully considered such that the benefits of using a new drug outweigh the risks in terms of the side effects caused by the drug. Damage to normal cells, tissues, organs and/or the whole organism is a big concern. Several tests are now routinely performed and are required for drug approval by various regulatory agencies around the globe. The primary goals of such preclinical safety evaluation of drugs are: (1) to identify an initial safe starting dose and subsequent dose escalation scheme to humans; (2) to identify potential target organs of toxicity and reversibility of toxicity; (3) to identify potential damage to the genetic material (genotoxicity); and (4) to identify parameters of clinical monitoring. In this paper, various models for genotoxicity assays are presented. These include: Ames assay, in vitro chromosome aberration assay and an in vivo micronucleus assay. New technologies, such as DNA adduct formation, DNA strand breakage, apoptotic changes, p53 gene expression and transgenic animal models, are also considered.
Serum Hyaluronan as a Marker of Liver Fibrosis in Hemophiliacs with Hepatitis C Virus-Associated Chronic Liver Disease
Authors: Yamada Masahiko , Fukuda Yoshihide , Nakano Isao , Katano Yoshiaki , Takamatsu Junki , Hayakawa Tetsuo
Published: April 2003

We measured serum type III procollagen peptide, type IV collagen (IV-C), and hyaluronan (HA) in 36 hemophiliacs with hepatitis C virus (HCV)-related chronic liver disease. We also measured these markers in 19 interferon (IFN)-treated patients before and after a 6-month course of IFN-α. The serum concentrations of IV-C and HA were correlated with the stage of fibrosis (IV-C r = 0.38; HA r = 0.78). These markers fell only in complete responders showing sustained clearance of serum HCV RNA by IFN. These results suggest that, in hemophiliacs with chronic liver disease, serum HA measurement might be an alternative to liver biopsy and reflect the response to IFN.
Accelerated Phase of Chronic Myeloid Leukemia Presenting with Hypercalcemia and a Mediastinal Mass
Authors: Quitt Miriam , Kelner Judith , Sova Janina , Froom Paul , Aghai Esther
Published: April 2003

A patient with chronic myeloid leukemia developed hypercalcemia as a presenting sign of the accelerated phase of the disease. Ultrasound of the neck showed a large hypodense mass connected to the thyroid gland, which was thought to be a parathyorid tumor and the cause of the hypercalcemia. Histology of the surgically removed mass revealed a chloroma. The patient’s course was complicated by respiratory failure and metastatic calcinosis of the lung, an unusual finding in hypercalcemia of short duration.
Combination Chemotherapy with G-CSF, M-CSF and EPO: Successful Treatment for Acute Myelogenous Leukemia without Blood Transfusion at Lower Medical Costs
Authors: Kaito K. , Kobayashi M. , Sakamoto M. , Shimada T. , Masuoka H. , Nishiwaki K. , Saeki A. , Sekita T. , Otsubo H. , Hosoya T.
Published: April 2003

A 55-year-old Jehova’s Witness was treated for acute myelogenous leukemia (AML) by intensive chemotherapy with enocitabine, 6-mercaptopurine and daunorubicin. G-CSF, M-CSF and EPO were subsequently administered. Even though no blood transfusion was given for religious reasons, complete remission was achieved without serious infection and hemorrhage. The total cost for induction chemotherapy was less expensive than is the case for elderly AML patients. This case indicates that the administration of cytokines might reduce the incidence of infection and the necessity for blood products, which would result in favorable cost effectiveness for the treatment of elderly patients with AML.
Pure Red Cell Aplasia Associated to Clonal CD8+ T-Cell Large Granular Lymphocytosis: Dependence on Cyclosporin A Therapy
Authors: Coutinho Jorge , Lima Margarida , dos Anjos Teixeira Maria , Cabeda José Manuel , Leite Fernanda , Justiça Benvindo
Published: April 2003

This case report details a single patient with pure red cell aplasia (PRCA) associated with clonal CD3+, TCRαβ+, TCR-Vβ8+, CD8+, CD57+ large granular lymphocytosis whose anaemia did not respond to conventional immunosuppressive therapy but did respond to cyclosporin A (CsA). The patient has become dependent on CsA for 7 years in order to control anaemia due to associated PRCA.
Mononeuropathy Multiplex in the Course of Idiopathic Thrombocytopenic Purpura
Authors: Yalçin Atilla , Avcu Ferit , Çetin Türker , Yeşilova Zeki , Beyan Cengiz , Kaptan Kürşad
Published: April 2003

We report the simultaneous occurrence of idiopathic thrombocytopenic purpura and mononeuropathy multiplex in a 21-year-old man. Electromyographic study revealed various axonal degenerative alterations in the right and left peroneal and right tibial nerves.
Synergetic Effects of Retrovirus IFN-alpha Gene Transfer and 5-FU on Apoptosis of Colon Cancer Cells
Authors: Sabaawy Hatem E. , Farley Tim , Ahmed Tauseef , Feldman Eric , Abraham Nader G.
Published: April 2003

Gene transfer has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells including the most primitive stem cells and cancer cells. Several investigators have reported on the clinical effects of interferon-α (IFN-α) or the combination of 5-FU plus IFN-α on patients with advanced colorectal carcinoma. Therefore, we examined the ability of a retrovirus-mediated IFN-α gene transfer to infect colon cancer cells COLO 201 and the effect of IFN-α gene expression alone or in combination with other chemotherapeutic drugs as 5-FU. IFN-α showed positive antitumor activity against COLO 201 cells, whereas 5-FU showed time- and concentration-dependent antitumor activity against COLO 201 cells. Furthermore, we demonstrated that combination therapy of IFN-α gene transfer and 5-FU resulted in enhancement of cancer cell lethality. The potentiation increased with higher concentrations of 5-FU by 1.5- to 2.1-fold. Our results suggest that retrovirus-mediated IFN-α gene transfer in COLO 201 cells resulted in functional gene expression as assessed by the levels of IFN-α mRNA and protein; furthermore, the combination of IFN-α gene transfer and 5-FU have additional effects on the induction of apoptosis. This finding provides an experimental basis for possible clinical therapy using retrovirus-mediated IFN-α gene transfer alone or in combination with other chemotherapeutic drugs for treatment of colorectal cancer.
Establishment and Characterization of a CD95 (Fas/Apo-1)-Negative Myeloma Cell Line
Authors: Kuribayashi Noriomi , Hata Hiroyuki , Yoshida Minoru , Sonoki Takashi , Nagasaki Akitoshi , Kimura Tatsuya , Harada Naoko , Matsuzaki Hiromitsu
Published: April 2003

Although expression of CD95 (Fas/Apo-1) on myeloma cells has been reported, its significance is not clearly understood. We established a myeloma cell line, KHM-11ad (11ad), from a parental cell line, KHM-11, by collecting cells adhered to a plastic dish. KHM-11 cells have been reported to be positive for CD45 and CD95 (Fas/Apo1), and negative for a myelomonocytic antigen, CD13. Interestingly, CD95 was not detected in 11ad. Expression of CD45 was also significantly decreased in 11ad cells while expression of CD13 was detected in these cells. The growth rate of 11ad cells was 1.7 times lower than that of KHM-11 cells. Analysis of adhesion molecules showed that expression of VLA4 and CD44 was significantly suppressed in 11ad. The IC50 of melphalan (L-PAM) for 11ad cells was 50 times higher than that for KHM-11, indicating that 11ad is significantly refractory to L-PAM than KHM-11 cells. Induction of apoptosis by doxorubicin and cycloheximide was suppressed in 11ad cells compared with those in KHM-11 cells. Western blot analysis for Bcl-2 family of proteins showed that Bax was expressed at a 2.2 times lower level in 11ad cells than in KHM-11 cells while there was no difference in expression of Bcl-2, Bcl-Xs nor Bcl-XL. These results suggest that CD95-negative myeloma cells may have characteristics as follows: (1) slow proliferation; (2) low sensitivity to apoptosis; (3) low expression of VLA4, CD44 and Bax. Although these intraclonal variations were based on the findings of cell lines, these may reflect similar variations in vivo. The 11ad line may be a suitable model for analyzing intraclonal variation of myeloma cells.
Transcripts of Immunoglobulin Germline Mu: An Amplified Myeloid and B-Lymphoid Common Gene Program in Various Leukemias
Authors: Dong Lujia , Guo Mei , Huang S.M. , Jia S.Q. , Wang Haitou
Published: April 2003

To investigate the clinical implications of germline Cµ transcription, the splice region between the 3′ end of the enhancer and the first exon of immunoglobulin germline μ was analyzed by RT-PCR in 63 samples from 59 patients with leukemia. Immunophenotypes of 33 samples from patients with acute leukemia were analyzed using a panel of these monoclonal antibodies: anti-immature/stem cell (HLA-DR, CD34); anti-mature myeloid (CD33, CD15); anti-T lymphoid (CD2, CD3, CD5, CD7, CD8), and anti-B lymphoid (CD10, CD19, CD20). Of the 63 samples, 33 (52%) contained germline Cµ transcripts: 2/2 patients with chronic lymphocytic leukemia; 17/26 (65.4%) patients with acute myeloblastic leukemia; all 4 patients with chronic myelogenous leukemia in blast crisis and 1 in accelerated phase; 9/12 patients with acute lymphocytic leukemia. A clear correlation between germline transcripts and HLA-DR expression was observed among germline-positive cases (p < 0.01). Cµ expression and response to therapy clearly indicated that germline-µ-positive leukemia patients responded poorly to chemotherapy and had a worse clinical prognosis compared with Cµ-negative patients (p < 0.01). After two courses of chemotherapy, 7/9 Cµ-negative patients achieved complete remission compared to only 7/29 Cµ-positive patients (p < 0.01). We conclude that the gene-regulating immunoglobulin germline Cµ may be amplified in myeloid and B-lymphoid cells during leukemogenesis. Such genetic changes may be correlated with cellular terminal differentiation injury, resistance to chemotherapy and uncontrolled malignant cell proliferation.
Automated Enumeration of Cellular Composition in Bone Marrow Aspirate with the CELL-DYN 4000TM Automated Hematology Analyzer
Authors: Sakamoto Chikao , Yamane Takahisa , Ohta Kensuke , Hino Masayuki , Tsuda Izumi , Tatsumi Noriyuki
Published: April 2003

The present study was designed to evaluate the automated analysis of bone marrow aspirates with the CELL-DYN 4000 (CD4000) hematology analyzer. Bone marrow aspirates were diluted twice with phosphate-buffered saline and assayed with the CD4000. The percentages of subpopulations including lymphocytes, neutrophils, and erythroblasts were obtained with the CD4000, and as a reference, differential counts by microscopic observation of May-Grünwald-Giemsa-stained films of bone marrow aspirate were performed (n = 48). Significant correlations (p < 0.0001) between the results with the two methods were obtained for total nucleated cell count, lymphocytes, neutrophils, erythroid cells, and the myeloid/erythroid ratio. The present method can provide quantitative data of bone marrow aspirate and will be useful in bone marrow screening.
Comparison of Different Lymphoma Cell Purging Modalities: An Experimental Study with K422 Lymphoma Cells
Authors: Hundsdörfer P. , Fruehauf S. , Haberkorn M. , Höft R. , Haas R. , Zeller W.J.
Published: April 2003

Blood-derived autografts from patients with non-Hodgkin’s lymphoma (NHL) are frequently contaminated with clonogenic lymphoma cells. In order to obtain a more efficient lymphoma cell depletion from the transplants we compared the efficiency of different purging techniques: B-cell-directed depletion, CD34+ selection by immunomagnetic beads (IMB selection) or by immunoadsorption with a biotin-avidin column (BAC selection). Furthermore, two combination approaches were investigated: IMB selection after B-cell depletion as well as BAC selection after B-cell depletion. To assess purging efficiency, fluorescence-tagged (PKH26) K422 follicular NHL cells were admixed to the respective samples of leukapheresis products. BAC selection following B-cell depletion compared to BAC selection alone showed no significant differences in CD34+ purity (77 ± 12.5% vs. 70.7 ± 5.4%) (mean ± SE) or CD34+ recovery (35.3 ± 8.5% vs. 32.8 ± 10.4%), but a significantly (p < 0.005) higher lymphoma cell purging efficiency (log 4.32 ± 0.15 vs. log 2.92 ± 0.19). IMB selection following B-cell depletion and IMB selection alone resulted in a CD34+ purity of 40.8 ± 8.7% and 64.7 ± 7.9%, a CD34+ recovery of 47.2 ± 8.3% and 26.5 ± 6.5% and a lymphoma cell purging efficiency of log 3.68 ± 0.16 and log 3.48 ± 0.21, respectively. Lymphoma cell purging efficiency after either CD34 selection method alone as well as after either double purging method was significantly higher (p < 0.0005 and p < 0.00005, respectively) compared to B-cell depletion alone (log 1.44 ± 0.23). Our results argue for the combination of different purging modalities to achieve a maximal lymphoma cell depletion.
A Patient with Multiple Myeloma, Amyloidosis and Light-Chain Deposition Disease in Kidneys with a Long Survival
Authors: Christou Leonidas , Hatzimichael Eleftheria Chr. , Sotsiou-Candila Florentia , Siamopoulos Konstantinos , Bourantas Konstantinos L.
Published: April 2003

We report a case of a 39-year-old man with λ-light-chain multiple myeloma, nephrotic syndrome due to λ-light-chain deposition disease in kidneys and amyloidosis in other tissues. The patient was treated with melphalan and prednisone for 1 year. After that, he was administered interferon-α2b (IFN-α2b; 3 MU, 3 times a week) as maintenance therapy for 2 years. At present, 5 years and 6 months after the initial diagnosis, the patient receives IFN-α2b (3 MU, twice a week) and remains in complete haematological remission.
The Delta-Globin RNA Transcript Level in Beta-Thalassemia Carriers
Authors: Huang Shu-zhen , Zeng Fan-yi , Chen Mei-jue , Ren Zhao-rui , Shen Min , Rodgers Griffin P. , Schechter Alan N. , Zeng Yi-tao
Published: April 2003

Increased levels of hemoglobin A2 (HbA2) are present in most β-thalassemia carriers. The mechanism of this effect is not understood, although the increase may result from transcriptional and posttranscriptional changes. In the present study, we quantitate δ-globin mRNA levels in peripheral-blood-enriched reticulocytes and characterize the variation of δ-mRNA levels in 30 β-thalassemia heterozygotes who individually carry one of the four common Chinese β-thalassemia alleles [codons 41/42 (–TTCT); codon 17 (A→T); IVS-II-654 (C→T); –28 (A→G)]. A sensitive and quantitative competitive reverse-transcriptase polymerase chain reaction method was developed and used to assess the absolute amounts of δ-mRNA transcripts in these peripheral erythroid cells. The results showed a large increase in δ-mRNA amounts in all the carriers examined (72.3 ± 9.0 amol/μg RNA) as compared with those in 12 controls (1.2 ± 0.2 amol/ μg RNA). There was a direct correlation between the δ-mRNA levels and types of β-thalassemia alleles; generally, the δ-mRNA levels are higher in heterozygotes for β⁰-thalassemia mutations than β+-thalassemia mutations. The δ-mRNA levels correlated inversely with hemoglobin and red cell indices but directly with HbA2 levels in heterozygotes of each of the group of β-thalassemia mutations. These results suggest that a greater impairment in β-globin gene expression results in increased transcription of δ-globin gene and in a higher level of HbA2.
Splenomegaly at a University Hospital Compared to a Nearby County Hospital in 317 Patients
Authors: Swaroop Jyothi , O’Reilly Robert A.
Published: April 2003

Splenomegaly and massive splenomegaly were diagnostically evaluated retrospectively at Stanford University Hospital in 147 patients over 8 years and compared to the nearby county hospital (Santa Clara Valley Medical Center; VMC) in 170 inpatients over 11 years. Hematologic diseases at Stanford (data for VMC in parentheses) occurred in 66% (35%; p < 0.001) of the patients with splenomegaly and in 84% (54%; p < 0.001) of those with massive splenomegaly. Hepatic diseases occurred in 9% (36%; p < 0.001) of the patients with splenomegaly and in 5% (29%; p < 0.001) of those with massive splenomegaly. Splenectomy was performed in 71% of the patients at Stanford and in 9% of those at VMC (p < 0.001). The combined Stanford-VMC series showed significant associations (p < 0.01): for hematologic diseases with massive splenomegaly, lymphadenopathy, and blood cytoses; for hepatic diseases with hepatomegaly, cytopenias as hypersplenism, and abnormal liver function tests, and for infectious diseases with fever.
Cladribine Treatment of a Patient with Hairy Cell Leukemia and Concomitant Multiple Sclerosis
Authors: Hilbe W. , Berger T. , Konwalinka G. , Thaler J.
Published: April 2003

This is the first report on a patient suffering from both multiple sclerosis (MS) and hairy cell leukemia. The patient was first treated with interferon-α. Due to disease progression two courses of cladribine were given resulting in an improvement of the clinical course of both diseases. Interestingly, it was possible to arrest and even ameliorate the progression of MS by administering as little as 30% of the dosage recently recommended for the treatment of this disease.
Embryonic Stem Cells Release Potentially Novel Hematopoietic Factors
Authors: Croizat Helena , Bouhassira Eric E.
Published: April 2003

We have observed that a severe decrease in the number of erythroid progenitor cells follows the long-term culture (LTC) of human primitive stem cells on an established mouse fibroblast feeder layer. This suggests that one, or several, factors necessary to support erythroid differentiation might be missing in these culture conditions. To improve the erythroid differentiation and stem cell output of LTCs, we have examined the hypothesis that the factors that regulate pluripotent stem cell proliferation and erythroid commitment can be found in media conditioned by embryonic stem (ES) cells. We have found that media conditioned by undifferentiated and differentiating ES cells can affect differentiation patterns in both short-term culture and LTC assays. Medium conditioned by undifferentiated ES cells increases the numbers of estimated LTC-initiating cells (est.LTC-IC) and potentiates granulocytic differentiation. In contrast, medium conditioned by ES cells undergoing differentiation increases the number of est.LTC-IC and is a powerful promoter of erythroid differentiation. In the presence of this medium, the number of erythroid progenitors generated after 5 weeks of LTC was increased up to 100-fold as compared with controls, and the number of est.LTC-IC was amplified up to 140-fold. These results offer a new approach for the identification of factors implicated in stem cell proliferation, self-renewal and commitment. In addition, the improved LTC conditions for the expansion of stem cells without reduction of their in vitro differentiation potential should be useful for a wide range of applications.
Calcification in Untreated Non-Hodgkin’s Lymphoma of the Jejunum
Authors: Ishikawa Takeshi , Kobayashi Yutaka , Omoto Atsushi , Adachi Yoko , Nakagawa Syuji , Kaneko Toshiro , Nishida Koichi , Miyamoto Yuji , Chimori Yoshiro , Yoshikawa Toshikazu , Kondo Motoharu
Published: April 2003

A 69-year-old Japanese female was admitted to our hospital due to a 2-month history of vomiting after eating. Examination of the small intestinal tract revealed a tumor with calcification in the inner portion, from the horizontal portion to the ascending portion of the duodenum, and jejunojejunostomy was performed. The pathological findings of the tumor gave a diagnosis of non-Hodgkin’s lymphoma, diffuse small cleaved cell (Working Formulation classification), B cell type, of the jejunum. Calcification is rarely found in untreated malignant lymphoma and 15 cases of untreated malignant lymphoma with calcification have been reviewed.
New Imaging Findings in a Patient with Central Nervous System Dysfunction after Bone Marrow Transplantation
Authors: Takatsuka Hiroyuki , Okamoto Takahiro , Yamada Shinji , Fujimori Yoshihiro , Tamura Shu , Wada Hiroshi , Okada Masaya , Takemoto Yoshinobu , Nishimura Hiroyuki , Tachibana Hisao , Kanamaru A. , Kakishita Eizo
Published: April 2003

Central nervous system disorders are an important complication of bone marrow transplantation (BMT). We have recently performed cerebral angiography to examine central nervous system dysfunction in a 22-year-old woman with acute lymphoblastic leukaemia who had undergone BMT. Angiography demonstrated multiple stenoses and occlusions in the peripheral branches of the anterior and middle cerebral arteries, a pattern similar to that seen in vasculitis. She was thought to most likely have cytomegalovirus (CMV) vasculitis, but other forms of vasculitis, such as angiitis-like-syndrome-associated graft-versus-host disease could not be excluded. This case suggests that CMV vasculitis may cause central nervous system dysfunction after BMT and that imaging studies may provide useful information about central nervous system disorders in these patients.