bluuebunny/crossref_metadata_2025 huggingface dataset:
Operative Therapy in Disease Progression and Local Recurrence of Renal Cell Carcinoma
Authors: Fischer Claus G. , Schmid Hans-Peter
Published: April 2003

When local recurrence or distant metastasis occurs, the question arises as to which therapeutic concept should be applied. In contrast to the data on systemic immunotherapy, there are no systematic studies on surgical management of metastasis. Local recurrence (a rare condition) is frequently resected, whereby a prolongation of life can be achieved in individual cases. The complete surgical resection of pulmonary metastases has been shown, in a number of studies, to achieve a survival rate of 5 years in up to 44% of the cases. There are only few data regarding resection of osseous metastases; although in this respect some studies have reported an average survival rate of 34 months, the indication for this condition has, up to now, usually been seen as palliative. The prognosis of liver or brain metastasis is unfavorable; the survival rates achieved with the help of surgical procedures are scarcely higher than those resulting from the spontaneous progression of metastatic renal carcinoma (12 months). Thus, there is an urgent need for further studies in order to define the indication for the surgical management of metastasis.
Therapy of Superficial Bladder Carcinomas
Authors: Otto T. , Krege S. , Noll F. , Rübben H.
Published: April 2003

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 × weekly, 5 × monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3–6 months after initial diagnosis. There is no need – except in clinical trials – for the administration of unverified or not admitted drugs.
Prognostic Factors for Carcinoma of the Prostate
Authors: Altwein J.E. , Luboldt H.J.
Published: April 2003

Prognostic factors for prostatic carcinoma should be significant, independent and clinically important. They should be of practical use, and their determination should be affordable in everday practice. Prognostic factors may be grouped into patient-related, tumor-related and treatment-related. They should meet certain requirements, such as possession of a clear biological significance, an adequate sample size (possibly more than 150 patients), no patient population bias, an adequate statistical test, such as Cox regression analysis, as well as optimized cut-off values and reproducibility. From a pathologist’s view, prognostic factors with established values are grade, margin involvement, capsular penetration, seminal vesical involvement, metastases and invasion of fat in needle biopsies. In contrast to this, factors with little value are, among others, zone location or nuclear shape. If these guidelines for assessment of prognostic factors are not met, the prognostic factors grow exponentially, as an individual patient can only belong to one prognostic group. If one considers all three categories of prognostic factors together, the clinical stage matters most despite all uncertainties. The same holds true for grading; particularly, the well-differentiated grades on biopsy cores have the drawback of being reflected in the specimen only infrequently. The use of biomarkers to give a better prognostic information is also disappointing, as only PSA and PAP have a reliable value among 28 biomarkers. It is of note that new biomarkers are continuously being discovered and examined, such as cyclin A or D. Due to these deficiencies in all three categories of prognostic factors for prostatic carcinoma, prognostic indices in the form of nomograms were constructed. But, if these indices are employed to answer the most important question at the time of diagnosis, i.e., ‘is this man a candidate for surveillance?’, neoadjuvant treatment plus irradiation, neoadjuvant treatment plus radical prostatectomy, perineal radical prostatectomy, because of a low probability of extracapsular extension or positive lymph nodes, adjuvant therapy after local treatment with curative intent as opposed to progression-based treatment or immediate systemic treatment, let alone intermittent endocrine manipulation, are not reliably possible. The outcomes of the few available studies based on prognostic factors should be studied carefully. If considered, a valuable new way of estimating artificial neural networks is a possibility to come to practical terms.
Hormonal Therapy of Prostate Cancer: Is There Any News?
Authors: Pummer Karl , Schmid Hans-Peter , Trummer Harald , Augustin Herbert , Hubmer Gerhart
Published: April 2003

Androgen ablative therapy was introduced in the early 1940s and, even today, has remained the golden standard for the treatment of advanced prostate cancer. During the past decades, a variety of improvements have been achieved which, however, primarily aimed at a better tolerance or improved acceptance of androgen deprivation. However, after almost six decades of hormonal therapy it is appropriate to ask whether progress was also made in terms of efficacy, particularly as far as prolongation of survival or quality of life is concerned. During the last few years, two therapeutic strategies, maximal androgen blockade and intermittent androgen suppression, have been considered true conceptual advances. However, despite tremendous efforts and a huge number of studies so far, these concepts appear to produce more questions rather than answers. Therefore, it seems appropriate to raise some critical issues of maximal androgen blockade and intermittent androgen suppression.
Apoptosis, Mitosis, p53, bcl2, Ki-67 and Clinical Outcome in Prostate Carcinoma Treated by Androgen Ablation
Authors: Szende B. , Romics I. , Torda I. , Bély M. , Szegedi Zs. , Lovász S.
Published: April 2003

A prospective study on 16 patients with advanced (stage III and IV) prostate cancer was carried out. TNM stage, general clinical status, serum PSA level, the histological type and Gleason’s grade of the tumor were registered. Total androgen blockade or single-drug therapy (flutamide) was performed. On average, 4.81 months after the start of therapy rebiopsy, serum PSA determination and general clinical examination were performed. Histologic examination before and after treatment of HE-stained slides, as well as apop-tag reaction to show apoptotic cells, p53, bcl2, and Ki-67 immunostaining. Clinical improvement manifested by regression or lack of progression was observed in 10 patients. Increase of the apoptotic index and decrease of the mitotic index was detected in these cases. Serum PSA level decreased in all patients except in 3 fatal cases. The 6 clinically nonresponders who died after the second biopsy did not show an increased apoptotic or decreased mitotic index. Ki-67 positivity correlated well with the mitotic activity. Mutant p53 expression was higher in patients in whom antiandrogen therapy was ineffective. The bcl2 expression was a characteristic of the tumors of patients who later died. These results show that the degree of induction of apoptosis in prostate carcinoma by hormonal therapy varies from case to case. A given prostate cancer patient’s response to therapy may be predicted by following apoptotic and mitotic activity, as well as Ki-67 and p53 expression in repeated biopsies.
Penile Prosthesis Implantation and Couple’s Satisfaction
Authors: Porena Massimo , Mearini Luigi , Mearini Ettore , Marzi Marco , Zucchi Alessandro
Published: April 2003

Objective: Implant surgery is the most acceptable curative choice for patients with erectile dysfunction and their partners, since the results are excellent with regard to the couple’s pleasure and the materials used are extremely manageable Materials and Methods: We performed 46 prosthesis implantations in patients with erectile dysfunction: in 22 patients we implanted soft prostheses; in 20 malleable prostheses; in 1 a mono-component prosthesis, and in 3 patients a tri-component model. All patients and partners were evaluated using a questionnaire. Results: We obtained a degree of satisfaction equal to 82% against 18% dissatisfaction due to a sensation of ‘unnaturalness’ report by the partner, with low perioperative and postoperative complications. Conclusion: In our opinion the degree of satisfaction of the patient is currently the only legitimate indicator to establish the effectiveness of therapy.
Tc-99m MAG3 Renal Studies: Renogram and Effective Renal Plasma Flow in Spinal Cord Injury Patients
Authors: Changlai Sheng-Pin , Bih Liu-Ing , Lin Ding-Bang
Published: April 2003

To determine whether years since injury, level of injury, degree of injury, gender, or age influence renal function in 66 spinal cord injuries (SCI) patients without urological complications, individual kidney effective renal plasma flow (ERPF) and radionuclide renogram (RR) were measured using technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3). The 176 individual kidneys included 84 kidneys with normal ERPF and RR, 48 kidneys with normal ERPF but abnormal RR, and 44 kidneys with abnormal ERPF and RR. The incidence of abnormal Tc-99m renal study results was higher in the kidneys of female patients (37/54, 68%) than of male patients (55/122, 45%) (p < 0.05). We found that Tc-99m MAG3 renal studies including ERPF and RR are safe and noninvasive urological screening tests for SCI patients.
Xanthine Stone in the Urinary Bladder of a Male Child
Authors: Kiss András , Berényi Mihály , Csontai Ágoston
Published: April 2003

Urinary tract calculi composed primarily of xanthine are rare both in adults and children. We describe the clinical presentation and management of a 3.5-year-old boy with hereditary xanthinuria (an autosomal recessive disorder of purine metabolism) and primary bladder calculus formed from xanthine. To our knowledge this case demonstrates a previously undescribed form of xanthinuria in childhood. Xanthine stones, although rare, should be considered in the diagnosis of urolithiasis.
Diffuse Metastasized Testicular Teratoma and Paraneoplastic Thyreotoxicosis
Authors: Derakhshani P. , Klotz T. , Heidenreich A. , Engelmann U.
Published: April 2003

Paraneoplastic syndromes are rare entities in patients with excessive HCG production. This has been attributed to the thyroid-stimulating hormone-like activity of HCG. In most cases hyperthyroidism remains subclinical. We report on a patient with diffuse metastasized malignant teratoma and thyreotoxicosis due to excessive levels of tumor-derived HCG. This complication of nonseminomatous germ cell tumors is associated with potential morbidity and the need for prompt recognition is stressed. Treatment consists of standard antithyroid medication and immediate cytoreductive chemotherapy to reduce the paraneoplastic stimulus. Evaluation of thyroid hormone levels in all patients with serum HCG levels exceeding 20,000 U/l is recommended.
Metastatic Malignant Melanoma Presenting as Bilateral Incidentalomas
Authors: Hakenberg Oliver W. , Pese Kim , Marshall Vilis R.
Published: April 2003

Incidentally discovered adrenal masses often pose a diagnostic challenge in the asymptomatic patient. The majority represent functional adrenal adenomas but primary or secondary malignancy must be considered. Bilateral incidentalomas are rare, and a case of asymptomatic bilateral adrenal melanoma metastases is presented. The diagnostic and treatment strategies relevant to this clinical problem are presented and discussed.
Dermoid Cyst in the Adrenal Gland
Authors: Kaneko Natsumi , Kubota Yoko , Nakada Teruhiro , Sasagawa Isoji , Yaguchi Hiromasa , Suzuki Hitoshi
Published: April 2003

The first case of a dermoid cyst arising from the unilateral adrenal gland is reported with special reference to its embryonal development and imaging analysis.
PML/RARα(+) Hypergranular Acute Promyelocytic Leukemia (M3) Developing into an M3 Acute Myelocytic Leukemia without PML/RARα
Authors: Ruiz-Argüelles Guillermo J. , Ruiz-Delgado Guillermo J. , Reyes-Núñez Virginia
Published: April 2003

The case of an adult with PML/RARα(+) hypergranular acute promyelocytic leukemia (M3) that evolved into a rapidly fatal M3 acute myelocytic leukemia without PML/RARα after a complete and molecular remission had been achieved, is presented. Only 7 such cases have been published in the literature. The possible origin of this either leukemic relapse or secondary malignancy is briefly discussed, focusing on the fact that this diagnosis could only be defined by adequate molecular biology studies in the leukemic cells.
Littoral Cell Angioma Associated with Portal Hypertension and Resected Colon Cancer
Authors: Steensma David P. , Morice William G.
Published: April 2003

Littoral cell angioma (LCA) is a rare vascular tumor of the spleen with an unknown etiology and unclear natural history. An association with synchronous malignancy has been described. We report the case of a 54-year-old woman who had progressive splenomegaly over 3 years following resection of a colon adenocarcinoma. The splenomegaly was associated with portal hypertension and severe thrombocytopenia. Splenectomy was performed, and the histologic and immunocytochemical features of the spleen specimen were consistent with LCA. The relationship between LCA and malignancy is reviewed.
In vitro Apoptotic Response of Freshly Isolated Chronic Myeloid Leukemia Cells to all-trans Retinoic Acid and Cytosine Arabinoside
Authors: Stagno Fabio , Guglielmo Patrizia , Consoli Ugo , Inghilterra Giovanna , Giustolisi Giada Maria , Palumbo Giuseppe Alberto , Giustolisi Rosario
Published: April 2003

Chronic myeloid leukemia (CML) is a hematological malignancy resulting from clonal expansion and massive accumulation of leukemic myeloid cells that retain differentiation and maturation capacity. Since CML cell accumulation has been related to apoptosis inhibition by the product of the BCR-ABL gene, attempts to eradicate leukemic cells would require therapeutic drugs able to overcome this inherent resistance. Here, we investigated in vitro the apoptotic effect of all-trans retinoic acid (ATRA) and cytosine arabinoside (ARA-C), employed alone, in combination or in sequence, on freshly isolated cells from 10 patients with chronic-phase CML. Our cell cultures showed that both ATRA and ARA-C were able to induce apoptosis in CML cells, even if ARA-C resulted more effective than ATRA. The combined use of ATRA and ARA-C seemed to have only an additive effect while the sequential use did not show any advantage. These in vitro observations indicate that ATRA and ARA-C may be effective in reducing CML cells through apoptosis induction, suggesting that it could be worthwhile to examine ATRA and ARA-C combinations in the therapy of CML.
Influence of α-Thalassemia Trait on the Prevalence and Severity of Anemia in Pregnancy among Women in Kuwait
Authors: Diejomaoh F.M.E. , Haider M.Z. , Dalal H. , Abdulaziz A. , D’Souza T.M. , Adekile A.D.
Published: April 2003

α-Thalassemia is very common in the Kuwaiti population, but its influence on anemia of pregnancy has not been previously investigated. We have screened a group of 59 anemic (Hb <11 g/dl) pregnant women for the α-thal-2 (–α-3.7 kb) deletion which is the commonest α-thal allele in this community, using a polymerase chain reaction method. A control group of 35 nonanemic (Hb ≥11 g/dl) pregnant women was studied for comparison. All the women were in the second or third trimester of pregnancy. Among the 94 women in both groups, 69 (73.4%) had a normal complement of α-globin genes (αα/αα), 18 (19.1%) were heterozygotes (–α/αα) and 7 (7.4%) were homozygotes (–α/–α) giving an allele frequency of 17.0%. Among the anemic group, there were 44 (74.6%) individuals with a normal genotype, 9 (15.3%) heterozygotes and 6 (10.2%) homozygotes. In the nonanemic group, the corresponding prevalence figures were 25 (71.4%), 9 (25.7%) and 1 (2.9%), respectively. The difference between these distributions was statistically significant (χ2 = 37.5, p < 0.0001). However, the mean Hb values were similar in heterozygotes, homozygotes and normal individuals. We, therefore, conclude that while the α-thal trait affects the prevalence of anemia among pregnant Kuwaiti women, it does not affect its severity.
Hypereosinophilia due to Myiasis
Authors: Navajas A. , Cardenal I. , Piñan M.A. , Ortiz A. , Astigarraga I. , Fdez-Teijeiro A.
Published: April 2003

We report the case of a 2-year-old boy with hypereosinophilia who presented with fever, muscle pain and heart, CNS and skin involvement. He was treated with steroids with partial response. Six months after diagnosis of hypereosinophilia, several scalp nodules were surgically removed and Hypoderma bovis larvae were found, which led to the diagnosis of cutaneous myiasis. Following removal of the larvae, the clinical and hematological manifestations returned to normal.
Primary Pneumocystis carinii Prophylaxis with Aerosolized Pentamidine after Bone Marrow Transplantation
Authors: Machado C.M. , Macedo M.C.A. , Medeiros R.S.S. , Massumoto C. , Silva A.C.M. , Castelli J.B. , Silva R.L. , Ostronoff M. , Dulley F.L.
Published: April 2003

Patients undergoing immunosuppressive therapy have a 21% risk of developing Pneumocystis carinii pneumonia (PCP) if no prophylaxis is used [1]. During the first 6 months after bone marrow transplantation (BMT), the recipients have an estimated 9% risk of developing PCP [2]. Standard prophylaxis with sulfamethoxazole and trimethoprim (SMX/TMP) daily or intermittent doses has been used effectively in transplant and other immunosuppressed patients [2–4]. However, poor compliance and undesirable myelotoxicity are expected with this schedule, especially if other myelotoxic drugs such as ganciclovir have to be administered. Aerosolized pentamidine (AP) has been considered an attractive alternative in AIDS patients who do not tolerate SMX/TMP because only 4% of the patients discontinue AP prophylaxis due to side effects [5].
Overproduction of Antiplatelet Antibody against Glycoprotein IIb after Splenectomy in a Patient with Evans Syndrome Resulting in Acquired Thrombasthenia
Authors: Fuse Ichiro , Higuchi Wataru , Narita Miwako , Watanabe Toru , Hattori Akira , Aizawa Yoshifusa
Published: April 2003

We treated a 33-year-old female with Evans syndrome. She received high dose gamma globulin, prednisolone, and azathioprine, and her platelet count transiently increased. After splenectomy, the platelet count markedly increased. However, the bleeding tendency worsened and the bleeding time was prolonged. A platelet defect, characteristic of thrombasthenia, was found. Antigen-captured ELISA and Western blotting revealed that the patient’s serum had an IgG autoantibody against platelet membrane glycoprotein IIb and the patient’s plasma inhibited normal platelet aggregation. These findings suggest that overproduction of the antiplatelet antibody is triggered by platelet recovery due to splenectomy and affects platelet function resulting in acquired thrombasthenia.
Role of Cytokines in Healing Chronic Skin Wounds
Authors: Nath Charlotte , Gulati Subhash C.
Published: April 2003

In the chronic wound, the normal cascade of inflammation, granulation and reconstruction phases of healing is interrupted. Cytokines are now known to orchestrate different biochemical mediators resulting in the restoration of the healing phases. Growth factors may play a significant role in stimulating wound repair by stimulating growth and proliferation. Since growth factors stimulate a variety of functions depending on cell type and wound stage and since wound-healing defects may occur at any phase of healing, a mixed combination of growth factors would be predicted to be more effective than a single factor. Factors that may modulate the action of growth factors include electrical stimulation, weight bearing, debriding and ischemia.
Rare Alteration of Genomic Structure or Expression of the DPC4 Gene in Myelogenous Leukemias
Authors: Kaneko Hiroto , Horiike Shigeo , Sasai Yuri , Iwai Toshiki , Nakao Makoto , Yokota Shouhei , Taniwaki Masafumi , Kashima Kei , Misawa Shinichi
Published: April 2003

We examined homozygous deletion, point mutation and expression of DPC4 gene, a recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of chronic myelogenous leukemia including 22 in the chronic phase, 3 in the accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous leukemia including 9 at the initial presentation and 10 at relapse. Polymerase chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single strand conformation polymorphism study for the entire coding region were carried out. Homozygous deletion or subtle mutation was not detected in any of the samples examined. However, 3 patients with various clinical phases showed a decrease of DPC4 expression. These results suggest that DPC4 alteration is not a crucial event in the development or the progression of myelogenous leukemias.
Haematological Effects of Oral Cobalamin Preparations on Patients with Megaloblastic Anaemia
Authors: Kondo Haruki
Published: April 2003

We investigated the haematological effects of a massive dose of oral cobalamin (vitamin B12) on patients with cobalamin deficiency anaemia who had severe anaemia with a few neurological impairments and found that oral treatment was almost as effective as conventional injection therapy. The recovery of haematological indices with oral cobalamin preparations was slightly slower than with parenteral preparations, although the subjective symptoms disappeared soon after the start of therapy. The results of this study indicate that oral treatment keeps the cobalamin body stores satisfactorily filled and might be useful for older patients in whom injecting might be difficult.
Double Esterase Staining andOther Neutrophilic Granule Abnormalities in 237 Patients with the Myelodysplastic Syndrome Studied by the Cancer and Leukemia Group B
Authors: Elghetany M. Tarek , Peterson Bercedis , MacCallum Jane , Nelson Douglas A. , Varney Judy F. , Sullivan Arthur K. , Silverman Lewis R. , Schiffer Charles A. , Davey Frederick R. , Bloomfield Clara D.
Published: April 2003

We investigated double (specific and nonspecific) esterase (DE) staining in marrow cells of 237 patients with the myelodysplastic syndromes (MDS). Additional abnormalities of neutrophilic granules were examined cytochemically and immunocytochemically for myeloperoxidase activity and antigen elastase, lactoferrin and CD15 granule-membrane glycoproteins. Abnormal DE staining (≥3% of all nucleated marrow cells) was present in 27% of patients with no difference among different MDS subtypes. However, the prevalence of high abnormal DE staining (≥10%) was significantly lower in refractory anemia with excess blasts in transformation (1%) compared to other MDS subtypes (12–15%; p = 0.004). The prevalence of other granule abnormalities was not statistically different in the DE normal and DE abnormal groups. Abnormal DE staining is relatively common among all MDS subtypes. High DE staining may identify a subgroup of patients with a lower grade MDS.
Analysis of Neurofibromatosis Type 1 Gene Mutation in Juvenile Chronic Myelogenous Leukemia
Authors: Watanabe Ichiro , Horiuchi Takahiko , Hatta Nobuaki , Matsumoto Mitsuru , Koike Kenichi , Kojima Seiji , Ohga Shouichi , Fujita Shigeru
Published: April 2003

The neurofibromatosis type 1 (NF1) gene has been considered to be a tumor suppressor gene, since the NF1 gene product downregulates the ras oncogene product (p21ras). In addition, children with NF1 show an increased incidence of myelogenous leukemia, including juvenile chronic myelogenous leukemia (JCML). We studied 8 Japanese JCML patients without NF1 for mutations in exons 21–36 of the NF1 gene by using polymerase chain reaction/single-strand conformation polymorphism analysis. This region was chosen because it includes two main hotspots in the NF1 gene as well as the functionally important domain, GTPase-activating protein-related domain, which mediates the downregulation of ras activity. One of the 8 JCML patients exhibited a G to T transversion at the third nucleotide of the codon GAG for Glu at amino acid residue 1699, which results in the heterozygous conversion to Asp (E1699D). This variation was detected neither in 65 healthy volunteers nor 50 NF1 patients. No other variations were detected in our JCML patients. We suggest that NF1 gene mutation does not occur frequently in JCML without NF1.
Expression of the Rh-Related Glycoprotein (Rh50)
Authors: Suyama Kimita , Lunn Ruth , Smith Barbara L. , Haller Stephanie
Published: April 2003

The Rh50 glycoprotein is suspected of being involved in Rh antigen expression. We prepared Rh50 cDNA from a human bone marrow library by polymerase chain reaction and then subcloned this cDNA into various vectors. The vector containing Rh50 cDNA produced a 30-kDa nonglycosylated form of Rh50 in a rabbit reticulocyte lysate system and produced partially glycosylated Rh50 (32 kDa) when microsomes were added to the system. COS-1 cells transiently transfected with the vector containing Rh50 cDNA produced partially glycosylated Rh50 (32 kDa) recognized by a Rh50-specific antibody. Surface expression of Rh50 in K562 cells was also detected by flow cytometry using mouse monoclonal antibody (2D10) specific to Rh50. Partially glycosylated Rh50 (32 kDa) was again isolated from the lysates of K562 cells metabolically labeled with [35S]-methionine or [3H]-mannose using anti-Rh50 antisera. These systems (K562 and COS-1 cells) should prove useful for studying the transport of Rh proteins within the cell and the necessary components needed for Rh antigenicity at the cell surface.
Human Parvovirus B19 Capsid Antigen in Granulocytes in Parvovirus-B19-Induced Pancytopenia after Bone Marrow Transplantation
Authors: Kobayashi Shoichi , Maruta Atsuo , Yamamoto Toshiharu , Katayama Noriko , Higuchi Ryuko , Sakano Yoko , Fujita Hiroyuki , Koharazawa Hideyuki , Tomita Naoto , Taguchi Jun , Kodama Fumio , Nakamura Yoshiyasu , Shimizu Akio
Published: April 2003

A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear.
Mixed Allogeneic Chimerism to Induce Tolerance to Solid Organ and Cellular Grafts
Authors: Exner BeateG. , Acholonu IjeomaN. , Bergheim Marianne , Mueller YvonneM. , Ildstad SuzanneT.
Published: April 2003

Transplantation of solid organs and cellular grafts has become clinical routine in the last 30 years. However, the requirement for life-long immunosuppression is associated with infections, malignancies and end-organ toxicity. Moreover, the treatment fails to prevent chronic rejection. The induction of donor-specific transplantation tolerance would solve these problems, but has remained an elusive goal. One approach to achieve transplantation tolerance is through hematopoietic chimerism. This review outlines different concepts of hematopoietic chimerism focusing on macrochimerism. Mixed allogeneic chimerism, also known as macrochimerism, is defined as engraftment of hematopoietic stem cells achieved by bone marrow transplantation (BMT). It discusses the advantages and limitations of the BMT as well as approaches to overcome these limitations in the future.
Influence of Aspirin on Platelet Count and Volume in Humans
Authors: Erhart Stephan , Beer Jürg H. , Reinhart Walter H.
Published: April 2003

Platelet volume and total platelet mass are parameters of platelet activity and have become a prognostic factor in coronary heart disease. We have studied the influence of aspirin on platelet count, volume and total platelet mass in vitro and in a randomized double-blind, placebo-controlled study in 20 healthy young male volunteers in vivo. Aspirin had no influence in vitro on either platelet count, volume or mass. Repeated blood sampling during a 7-day treatment with 250 mg aspirin daily showed an increased platelet count (7.3% on day 1, 3.0% on day 2, 6.8% on day 4 and 9.3% on day 7; p < 0.01) and total platelet mass (7.2, 5.0, 8.6 and 11.5% on days 1, 2, 4 and 7, respectively, p < 0.01). Aspirin treatment without repeated blood withdrawal had no effect. These data indicate that aspirin may affect the circulating platelet mass under certain conditions.
High Incidence of Transiently Appearing Complement-Sensitive Bone Marrow Precursor Cells in Patients with Severe Aplastic Anemia - A Possible Role of High Endogenous IL-2 in Their Suppression
Authors: Nissen Catherine , Tichelli André , Gratwohl Alois , Warthmann Christoph , Moser Yolanda , dalle Carbonare Verena , Sendelov Silvia , Chklovskaia Elena , Jansen Wendy , Wodnar-Filipowicz Aleksandra , Sadallah Salima , Speck Bruno
Published: April 2003

In a prospective long-term study on the incidence of paroxysmal nocturnal hemoglobinuria (PNH), 115 consecutive patients with severe aplastic anemia (SAA), 97 treated with antilymphocyte globulin (ALG) and 18 with bone marrow transplantation (BMT), were observed over a period of 4–18 years and tested for the presence of complement-sensitive hematopoietic precursor cells with the bone marrow (BM) sucrose test. Sixteen (14%) of the ALG-treated patients developed clinical signs of PNH between 0.5 and 8 years after treatment. Complement-sensitive BM precursors were found in 89% of the SAA patients at some time during their disease, but in none of 18 normal donors. At diagnosis, their proportion was significantly higher in patients who later developed PNH than in patients who later achieved disease-free complete remission (CR). After ALG, the abnormal population was found in both groups, but it was gradually replaced by normal precursors in remission patients. After BMT, the complement-sensitive population decreased to very low numbers in patients with a stable graft, but increased again in 3 patients upon graft rejection. Mimicking the PNH defect by enzymatic removal of glycosyl-phosphatidylinositol (GPI)-linked proteins from CD34+ cells resulted in their complement sensitivity, suggesting that the BM sucrose test identifies precursor cells carrying the PNH defect. In 66 patients, white blood cells (WBC) in peripheral blood (PB) were examined for GPI-deficient populations by flow cytometry (FACS). Ten patients with signs of clinical or laboratory PNH had over 25% complement-sensitive precursor cells in the BM and a GPI-deficient WBC population in the PB. Of 56 SAA patients without PNH, 8 had an abnormal population detectable with both tests, 26 only with the BM sucrose test, 4 only with PB FACS analysis, and in 18, no abnormal cells were detected with either test. In search for parameters which might explain why in some patients the abnormal population expands, while it regresses or disappears in others, we tested the release of IL-2 as a parameter of immune competence. At diagnosis, IL-2 release was approximately 50% of normal in patients who later developed PNH, while it was double the normal value in patients who later achieved CR. We conclude that the majority of SAA patients transiently harbor complement-sensitive precursor cells in the BM. Patients with more than 25% abnormal BM precursors and low endogenous IL-2 release are at risk of progression to clinical PNH.
wt1 Gene Expression in Childhood Leukemias
Authors: Niegemann Eckhard , Wehner Sibylle , Kornhuber Bernhard , Schwabe Dirk , Ebener Uwe
Published: April 2003

The expression of the Wilms’ tumor gene (wt1) was detected in various tissues during embryonic development. Mutations in the wt1 gene probably play an important role in certain tumors, e.g. the Wilms’ tumor. Furthermore the expression of wt1 gene was found in some human leukemias. In the present study we investigated the expression of wt1 gene in several types of childhood leukemia by reverse transcriptase-polymerase chain reaction. Bone marrow or peripheral blood of 61 pediatric patients (48 at initial diagnosis, 13 at first or second relapse) were analyzed. wt1 gene expression was detected in 35/48 patients (73%) with newly diagnosed leukemias and in 12/13 cases (92%) who had suffered from relapse. The expression levels were higher for AML than for ALL. The frequency of wt1 expression in different subtypes of acute leukemia was compared with results found in adult patients. Our results show that the frequency of wt1 gene expression in acute childhood leukemias is similar to previous data reported for adults.
Thrombotic Thrombocytopenic Purpura during Interferon Alpha Treatment for Chronic Myelogenous Leukemia
Authors: Lacotte L. , Thierry A. , Delwail V. , Dreyfus B. , Guilhot F.
Published: April 2003

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome have recently been observed in patients undergoing interferon alpha (IFN-α) therapy. However, the relationship between disease and therapy has not been established, essentially because of concomitant treatment or previous bone marrow transplantation. We present a case of TTP developing during IFN-α therapy for chronic myelogenous leukemia. In this case, IFN-α seems to be the only etiological agent.
Paroxysmal Nocturnal Haemoglobinuria: A Replacement of Haematopoietic Tissue?
Authors: Schrezenmeier Hubert , Hildebrand Anette , Rojewski Markus , Häcker Hans , Heimpel Hermann , Raghavachar Aruna
Published: April 2003

Acquired somatic mutations of the PIG-A gene lead to deficient expression of glycosyl-phosphatidyl-inositol-anchored proteins (GPI-AP) by haematopoietic cells and play a causative role in the pathogenesis of paroxysmal nocturnal haemoglobinuria (PNH). However, PIG-A mutations do not explain how the defective PNH clone can expand. It was hypothesized that a selection process conferring a relative advantage to the GPI-AP-deficient population is required. Since GPI-AP-deficient cells are also detectable in a substantial proportion of patients with otherwise typical aplastic anaemia (AA), the mechanisms inducing bone marrow failure might selectively spare the GPI-deficient cells. In order to examine the growth characteristics of GPI-AP-deficient cells in more detail, we performed repeated analyses of GPI-AP expression on peripheral blood cells in 41 patients with AA. We observed four patterns of the course of GPI-AP-deficient populations: (1) 13 patients showed normal expression of GPI-AP in the first analysis and in at least two follow-up studies at a median time of 709 days after the first analysis. (2) Secondary evolution of a GPI-AP-deficient population was a rare event. Only 4 patients with initially normal GPI-AP expression developed a GPI-AP-deficient population during follow up after immunosuppressive treatment. (3) Persistence of GPI-AP-deficient cells was observed in 16 patients during a median follow-up time of 774 days. However, in some patients, the size of the GPI-AP-deficient population increased substantially. (4) Disappearance of a GPI-AP-deficient population was observed in 8 patients. The time course of GPI-AP expression in relation to the treatment suggests that therapeutic interventions might modulate the ratio of normal versus GPI-AP-deficient haematopoiesis. Overall, these data argue against an ‘absolute growth advantage’ of GPI-AP-deficient cells. Our data are consistent with the hypothesis that haematopoietic failure caused by damage to normal haematopoiesis allows the outgrowth of a GPI-AP-deficient population. Thus, in at least some patients GPI-AP-deficient cells might pre-exist at a very low percentage and replace haematopoiesis after an insult to the normal cells.
Predictive Factors for Cure after Immunosuppressive Therapy of Aplastic Anemia
Authors: Viollier Romaine , Tichelli André
Published: April 2003

In a previous study, we evaluated efficacy of repeated antilymphocyte globulin (ALG) treatment for patients with severe aplastic anemia not responding to an initial ALG treatment or relapsing after initial response to ALG. We now searched in the same cohort of patients for differences between patients who responded to treatment and remained free of complications and those who relapsed or developed a clonal complication. From 107 patients surviving for more than 1 year after immunosuppression, 34 remained free from complications after the first course of ALG, and 73 presented an event defined as relapse of aplastic anemia, development of a clonal complication such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome or leukemia, or appearance of a solid tumor. We compared these two groups for survival, clinical performance and blood counts during follow-up. Survival probability was 93% for the event-free patients, and 55% for the patients with a complication event (p = 0.0003). Event-free patients had a higher incidence of complete remission (71%), were more often free of immunosuppressive treatment (79%) and independent of transfusions (100%), and had a higher Karnofsky score (91% with a score ≥90%) as compared to the group with events (29, 37, 67, 48%; p ≤ 0.0002). At 1 and 3 years, event-free patients had significantly higher leukocyte and neutrophil counts, as compared to patients with a complication (p < 0.05). However, at 3 and 5 years, event-free patients had borderline higher platelet counts (p = 0.056, p = 0.078) and hemoglobin (p = 0.097, p = 0.061). The coefficient of variation as an expression of the variability of the results in each group was systematically lower at 3, 5 and 10 years in the group of event-free patients. Despite some differences between the two groups, our data support the hypothesis that patients with long-lasting remissions should not be considered as definitively cured of aplastic anemia.
New Rearrangement Pattern after Treatment of Hairy-Cell Leukemia with 2-Chlorodeoxyadenosine
Authors: Schirmer Michael , Haun Margot , Grünewald Kurt , Geisen Francoise , Hilbe Wolfgang , Thaler Josef , Konwalinka Günther
Published: April 2003

Leukemic hairy cells are clonally proliferating B-lymphoid cells with clonal rearrangements of genes for immunoglobulin chains. We describe a patient with a new hairy-cell clone after treatment with 2-chlorodeoxyadenosine (2-CdA). In this patient, a single course of 2-CdA resulted in good partial remission of hairy-cell leukemia, but Southern blot analysis of bone marrow biopsies and polymerase chain reaction using seminested amplifications with consensus primers revealed a new rearranged band 4 months after therapy with 2-CdA. Four years after therapy, the patient is in complete clinical remission and both bands disappeared during follow-up. The new rearranged band might have been related to prior treatment of hairy-cell leukemia with 2-CdA.
Prevalence of the C677T Methylenetetra- hydrofolate Reductase Mutation in Thai Patients with Deep Vein Thrombosis
Authors: Angchaisuksiri Pantep , Pingsuthiwong Sarinee , Sura Thanyachai , Aryuchai Katcharin , Busabaratana Manisa , Atichartakarn Vichai
Published: April 2003

We investigated the prevalence of a genetic variation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) using polymerase chain reaction techniques in a sample of 500 general Thai population and among 40 unselected Thai patients with an objectively confirmed history of deep vein thrombosis (DVT). The prevalence of the mutated homozygous and heterozygous C677T MTHFR genotype in the group of 500 healthy Thai population was 1.4 and 25.6%, respectively (allele frequency of 14.2%). Of the 40 patients studied, none were homozygotes and 15% were heterozygotes for the C677T MTHFR gene mutation (allele frequency of 7.5%). There was no significant difference in genotype frequency between patients and control groups (p = 0.09). Odds ratios for the probability of the C677T MTHFR gene mutation in the patient versus control group were 0.49 (95% CI 0.21–1.12). These data indicated that the C677T MTHF gene mutation was not associated with DVT in the Thai population. The lower frequency of the C677T MTHFR gene mutation in our Thai population compared with reports from other studies suggests a wide heterogeneity in the 677T MTHFR genotype frequencies of the different ethnic populations even among Asians.
CD5+ Immunophenotype in the Bone Marrow but Not in the Peripheral Blood in a Patient with Hairy Cell Leukemia
Authors: Usha Lydia , Bradlow Basil , Stock Wendy , Platanias Leonidas C.
Published: April 2003

We report the case of a patient with rare CD5+ hairy cell leukemia, which was unusual, as there was also a discrepancy between the bone marrow and peripheral blood immunophenotypes. We propose that some degree of maturation within the malignant clone and the predominance of more mature CD5– hairy cells in the peripheral blood can explain this observation. The patient was treated with a conventional course of cladribine (2′-chlorodeoxyadenosine) and achieved complete remission. We conclude that the unusual CD5+ immunophenotype of this patient did not affect prognosis or change the response to standard therapy.
Effect of Chronic Fluoride Exposure in Uremic Rats
Authors: Dunipace Ann , Brizendine Edward , Wilson Marie , Zhang Wu , Wilson Cynthia , Katz Barry , Kafrawy Abdel , Stookey George
Published: April 2003

This study was conducted to test the hypothesis that the margin of safe fluoride exposure is narrowed in rats that are physiologically compromised by renal dysfunction. The study objective was to determine whether increases in fluoride retention and tissue fluoride levels in rats with surgically induced renal insufficiency result in toxic fluoride effects not ordinarily observed in healthy animals. Uremic and sham-operated control rats received 0 µg/ml, 5 (0.26 mmol/l), 15 (0.79), or 50 µg/ml (2.63 mmol/l) of fluoride in their drinking water for 3 or 6 months. Fluoride retention was monitored, and, following euthanasia, tissue fluoride and biochemical markers of tissue function were analyzed. Selected tissues were saved for histology, and bone marrow cells were harvested for determining the frequency of sister chromatid exchange, a marker of genetic damage. In spite of significantly higher levels of fluoride in the tissues of the animals with renal insufficiency, there were no clinically adverse, fluoride-induced, extraskeletal physiological, biochemical, or genetic effects of chronic exposure to common levels of fluoride in these rats.
Detection of Activated Plateletsin Urine by Double Immunofluorescence in Children with IgA Nephropat hy
Authors: Kamitsuji Hidekazu , Nakajima Mitsuru , Kawahara Shingo , Nishimura Tatsuo
Published: April 2003

The relationship between the activation of platelets (PLT) in urine and renal histological findings in children with IgA nephropathy (IgAN), thin basement membrane disease (TBMD), and minimal-change nephrotic syndrome (MCNS) was examined. The ratio of activated PLT to total PLT (activated and nonactivated PLT) was examined by double immunofluorescence using rhodamine-conjugated P selectin antibody (activated PLT) and fluorescein isothiocyanate conjugated PLT membrane glycoprotein antibody (GPIIb/IIIa, total PLT); the effect of urine on activation on PLT was also investigated. The number of activated PLT and the ratio of activated PLT to total PLT in urinary sediments were significantly higher in children with IgAN with diffuse mesangial proliferation than in those with TBMD or MCNS. PLT were activated by addition of urine in 13 out of 27 children with IgAN, and the activity was higher in the urine of those with active glomerular or interstitial lesions, while the urine of children with TBMD or MCNS had no effect. The presence of activated PLT and the effect of urine on PLT activation may be associated with the active glomerular or interstitial lesions in IgAN.
High-Energy Shock Waves Alter Cytosolic Calcium Mobilization in Single MDCK Cells
Authors: Jan Chung-Ren , Huang Jong-Khing , Tseng Ching-Jiunn
Published: April 2003

The damaging effect of shock waves on intracellular calcium homeostasis in renal tubular cells has not been investigated previously. We have examined the effects of shock waves on Madin Darby canine kidney (MDCK) cells by determining the release of two cellular enzymes: glutamate oxalactate transferase (GOT) and lactate dehydrogenase (LDH); and both the basal cytosolic calcium concentration ([Ca2+]i) and the [Ca2+]i rises evoked by Ca2+-mobilizing agonists after shock wave exposure (SWE). Immediately but transiently after SWE, the release of GOT and LDH increased by 15% and 5-fold, respectively, implicating cell membrane damage; and within 1–7 h after SWE, basal [Ca2+]i was elevated by 15–141%. In SWE-treated cells, the peak amplitude of the [Ca2+]i transients evoked by ATP, bradykinin, thapsigargin and 2,5-Di-(t-butyl)-1,4-hydroquinone (BHQ) was slightly altered, and the plateau amplitude was markedly elevated. The ATP and bradykinin receptors, the Ca2+ pump on the endoplasmic reticulum membrane, and the effector molecules involved in regulating the [Ca2+]i transients were slightly affected. Shock waves appeared to cause a mild impairment in the mechanisms responsible for the decay of the evoked [Ca2+]i rises.
Castleman’s Disease and Mesangial Proliferative Glomerulonephritis: The Role of Interleukin-6
Authors: Lui Sing-Leung , Chan Kwok-Wah , Li Fu-Keung , Cheng Ignatius K.P. , Chan Tak-Mao
Published: April 2003

Renal complications of Castleman’s disease (angiofollicular lymph node hyperplasia) are uncommon. The reported cases are very heterogeneous and their renal pathology ranged from minimal change disease, mesangial proliferative glomerulonephritis, to amyloidosis. We have previously reported two cases of Castleman’s disease with renal complications. We now present two more such cases. In contrast to other reports, all our cases are of the plasma cell type and their renal pathology showed remarkable similarities, namely mesangial proliferation, interstitial plasma cell infiltration and negative immunofluorescence. The level of serum interleukin-6 (IL-6) in both patients was elevated at presentation and came down with immunosuppressive therapy.