bluuebunny/crossref_metadata_2025 huggingface dataset:
Mild Beta-Thalassemia intermedia Caused by Compound Heterozygosity for Gγ(Aγδβ)o/β-Thalassemia and Molecular Characterization of the Defect in Four Chinese Families
Authors: Tan Jin Ai Mary Anne , Yap Sook Fan , Tan Kim Lian , Wong Yean Ching , Wee Yong Chui , Kok Juan Loong
Published: July 2003

Molecular characterization of the compound heterozygous condition – Gγ(Aγδβ)o/β-thalassemia – in four families showing mild β-thalassemia intermedia was carried out using DNA amplification techniques. Using the Amplification Refractory Mutation System (ARMS) to confirm the β-mutations and DNA amplification to detect the 100-kb Chinese-specific Gγ(Aγδβ)o-deletion, two families were confirmed to possess Gγ(Aγδβ)o/β-thalassemia with the IVSII No. 654 β+-allele. In the third family, the Gγ(Aγδβ)o-deletion was confirmed in the father and the mother was a β-thalassemia carrier with the cd 41–42 βo-allele. Their affected child with Gγ(Aγδβ)o/β-thalassemia was found to be transfusion dependent. The same Gγ(Aγδβ)o-deletion and β-thalassemia (cd 41–42) was also confirmed in a fourth family. In addition, the mother was also diagnosed with Hb H disease (genotype -α3.7/–SEA). Both the children were found to possess Gγ(Aγδβ)o/β-thalassemia but they were not transfusion dependent and this could be due to co-inheritance of α-thalassemia-2 (genotype-α3.7/αα) in the children together with their compound heterozygous condition.
Presence of a Bone Marrow Stromal Cell Line with Myoid Differentiation in Reactive Plasmacytosis and Plasma Cell Myeloma
Authors: Papadopoulos N. , Kotini A. , Skaphida P. , Jivannakis T. , Cheva A. , Tamiolakis D.
Published: July 2003

The presence of myoid cells (MCs) – stromal cells with myogenic differentiation – in human bone marrow (BM) has been observed during hematopoiesis in embryonic life, whereas during adult life, it is strictly related to various pathologic conditions. The aim of this study was to examine the presence, distribution and quantitation of cells in the stroma of the BM expressing α-smooth muscle actin (α-SMA) in reactive BM plasmacytosis and plasma cell myeloma. For this reason, a series of 10 trephine BM biopsies from patients with plasma cell myeloma and 10 specimens from healthy controls with reactive plasmacytosis were examined for the presence of stromal cells with myoid differentiation, using a monoclonal antibody recognizing α-SMA. Our results suggest that the incidence of MCs and subsequent fibrosis rises in plasma cell myeloma and in a lesser degree in the BM stroma of individuals with reactive plasmacytosis.
Cerebral Involvement as the Initial Manifestation of Chronic Lymphocytic Leukaemia
Authors: Kaiser Ulrich
Published: July 2003

A 53-year-old man presented with focal jacksonian seizures that were due to cerebral tumour manifestations. Stereotactic biopsy revealed infiltration by lymphocytes compatible with the diagnosis of chronic lymphocytic leukaemia (CLL). Simultaneously, Binet stage II CLL with bone marrow infiltration was diagnosed. Cranial radiotherapy with 36 Gy was performed. One year after diagnosis, the patient is in stable disease. Cerebral involvement is rare but may occur in early CLL. Cranial radiotherapy may lead to lasting remission. In case of spinal fluid involvement intrathecal chemotherapy is recommended.
Development of Secondary Anaplastic Oligoastrocytoma after Matched Unrelated Bone Marrow Transplantation in a Child with Acute Myeloid Leukemia
Authors: Panigrahi Soumya , Das Mayukh , Stagler Dalia , Konstantini Shlomi , Gmori Moshe , Slavin Shimon , Nagler Arnon
Published: July 2003

The growing incidences of secondary malignancies in long-term survivors of childhood leukemia following allogeneic bone marrow transplantation (alloBMT) are increasingly being reported. Among the late complications of conventional myeloablative alloBMT, the occurrence of secondary malignant solid tumors is of major concern. Secondary malignant and benign brain tumors such as astrocytoma, meningioma and glioblastoma have been described in long-term survivors of conventional myeloablative alloBMT. Here we report a case of secondary anaplastic oligoastrocytoma that developed 7 years after matched unrelated alloBMT for relapsing childhood acute myeloid leukemia (AML) with CNS involvement. Although isolated CNS relapse of primary leukemia following alloBMT is not uncommon, it is important to identify and define potential risk factors that may lead to the development of secondary brain tumors in children who received high-dose chemotherapy and irradiation prior to alloBMT presenting with progressive neurological symptoms and to differentiate them from leukemia relapse with CNS involvement.
A Case of Leukemia of the Appendix Presenting as Acute Appendicitis
Authors: Toubai Tomomi , Kondo Yoko , Ogawa Takahumi , Imai Akitoshi , Kobayashi Naoki , Ogasawara Masahiro , Kiyama Yoshio , Higa Toshio , Sato Keisuke , Miyokawa Noriyuki , Tanaka Junji , Imamura Masahiro , Kasai Masaharu
Published: July 2003

A 71-year-old man was admitted to our hospital because of right lower abdominal pain. He was suspected of having acute appendicitis and soon after admission, appendectomy was performed. Macroscopically, the appendix was greatly swollen and reddened, but had no abscess. Microscopically, polymorphonuclear leukocytes were not found, but diffuse infiltration of atypical cells was observed. Examination of a bone marrow aspirate revealed 74% blasts that were peroxidase stain positive. We diagnosed acute myelogenous leukemia (FAB classification, M2). He received induction chemotherapy, but died 49 days after admission. Leukemic cell infiltration of the appendix is rare and acute appendicitis as the initial manifestation of leukemia is even rarer.
Successful Treatment of B Cell Chronic Lymphocytic Leukemia-Associated Severe Paraneoplastic Pemphigus with Cyclosporin A
Authors: Gergely Lajos , Váróczy László , Vadász Györgyi , Remenyik Éva , Illés Árpád
Published: July 2003

Since the first description of paraneoplastic pemphigus, several cases have been described in the literature. However, curative therapy is usually a challenge to the physicians treating this disease. Several publications are available discussing the efficacy of steroids, cyclophosphamide and cyclosporin A. Recently, a report of the successful use of rituximab was also published. However, the use of cyclosporin A is controversial in the case of B cell malignancies, as there are reports showing the cytotoxic effect of this drug on B cells. However, other authors report no effect, or even unwanted effects resulting in B cell proliferation. We report the case of a 50-year-old Caucasian male. He developed a B cell lymphoma consisting of CD5/CD20-double-positive cells, and 2 months later, it was followed by a very severe paraneoplastic pemphigus affecting the mucosa and the skin. The lymphoma was well managed with CHOP and CVP polychemotherapy, followed by oral chlorambucil; however, the bullous eruptions did not disappear. Oral steroids, cyclophosphamide, plasmapheresis and IVIG therapy were only partially successful, so we decided to use oral cyclosporin A. Starting with 7 mg/kg and maintaining a steady plasma level of no less then 110 ng/l, the bullae completely disappeared within 6 weeks, and the patient has been in remission for 17 months now, taking the oral cyclosporin A continuously. The underlying B cell disorder did not relapse during the therapy.
Sentenced to Treatment: Early Experience of Drug Treatment and Testing Orders in England
Authors: Finch Emily , Brotchie Janet , Williams Karen , Ruben Sue , Felix Lorna , Strang John
Published: July 2003

Drug Treatment and Testing Orders (DTTOs) were introduced in the 1998 Crime and Disorder Bill and were piloted in three areas in England over the subsequent 18 months. The orders, funded by the Home Office, allow drug using offenders to be coerced into attending for treatment, to have regular urine tests and to be reviewed by the courts. In Croydon an equal partnership was set up between probation, a local statutory provider of drug services and a voluntary sector agency. Treatment plans were individualised and included a variety of treatment options. Forty-eight orders were imposed mainly for persistent shoplifting. Sixty-three percent of individuals had used heroin and 54% crack cocaine in the 30 days before the order was imposed. Ethical issues raised in coerced treatment were important for the individuals providing treatment although the clients all had to consent to treatment. The pilot programme raised issues about the nature of treatment, clinical responsibility, the selection of clients for orders and the objectives of treatment. Frequent urine testing was problematic but in the vast majority of cases clients were not breached just because of positive tests. The provision of DTTOs in an area created unacceptable inequalities in access to treatment. The paper concludes that partnership working and clear objectives are vital for treatment programmes to operate effectively. More research is needed to explore the most optimum way to deliver treatment in the context of a DTTO.
Are Amniotic Fluid Alpha-Fetoprotein Levels Influenced by the Gender in Twin Pairs?
Authors: Sharony Reuven , Drugan Arie , Amiel Aliza , Grinshpun-Cohen Julia , Markov Shlomo , Fejgin Moshe D.
Published: July 2003

Objectives: To examine the assumption that amniotic fluid alpha-fetoprotein (AFAFP) levels are different in female and male twin fetuses. Design: Amniotic fluid levels of AFP in pregnancies with female and male fetuses in gender-concordant and gender-discordant twins were compared. A t test of p < 0.05 was considered significant. Material and Methods: Between 1995 and 1999, 332 genetic amniocenteses on twin pregnancies were performed at Meir Hospital, Kfar Saba, and Rambam Hospital, Haifa, Israel. One hundred and sixty-six were concordant for gender (84 females and 82 males) while 166 pairs differed in their gender. The amniotic fluid AFP levels of each sac were measured using fluorescent immunoassay methods by an AutoDELFIA machine. Results: The mean levels of AFAFP were lower in female twins compared to their male counterparts in same-gender twins (p = 0.07), although the difference was quite small. Nevertheless, there was no such difference between AFAFP of male versus female fetuses in gender-discordant twins. Conclusions: The levels of AFAFP were higher in the male twins of gender-concordant twins in comparison to female twins. No such difference was found between female versus male fetuses in gender-disconcordant twins.
Clinical and Pressure-Flow Changes after Long-Term Treatment with Alfuzosin SR
Authors: De Nunzio C. , Franco G. , Iori F. , Leonardo C. , Minardi V. , Laurenti C.
Published: July 2003

Objectives: The aim of our study was to evaluate the symptomatic and urodynamic changes after 1–5 years of treatment with alfuzosin in patients with benign prostatic hyperplasia. Methods: Out of 255 patients with lower urinary tract symptoms observed from 1992 to 1997, who completed the International Prostatic Symptom Score (I-PSS) and underwent full urodynamic investigation, 161 were found to be obstructed (Schäfer classes 2–6). One hundred and two subsequently consented to a second clinical and urodynamic evaluation. Out of these, 46 underwent surgical treatment, 20 were elected for watchful waiting (WW) and 36 received a medical treatment. Twenty out of these, with a mean age of 65 years, a mean prostatic volume of 44 ml (20–70) a median Schäfer’s obstruction class of 3 (range 2–5) were treated with slow release alfuzosin 5 mg twice a day. We re-evaluated these 20 patients with a second I-PSS and pressure-flow study after 1–5 years (mean: 2 years) of treatment. The patients in the WW group with comparable baseline characteristics were considered as controls. The Wilcoxon matched-pairs signed rank test and the Kruskal-Wallis test were used for statistical analysis. Results: In the group treated with alfuzosin, no differences were noted for I-PSS (14.9 ± 6,8; 13.3 ± 5); maximum flow (124 ± 6; 14 ± 6) and projected isometric pressure (105 ± 36; 105 ± 26). Statistically significant differences were noted for residual urine (103 ± 100; 33 ± 38, p = 0.02); detrusor pressure at maximum flow (64.4 ± 23; 53 ± 12, p = 0.04), minimum urethral opening pressure (36.5 ± 9; 31 ± 9, p = 0.02), Schäfer class (2.7 ± 0.7; 2 ± 0.8, p = 0.04); urethral resistance algorithm (34.7 ± 11; 27 ± 7, p = 0.02). Statistically significant differences between baseline and follow-up were noted for none of the clinical and urodynamic parameters in the WW group. Conclusions: Patients with bladder outlet obstruction seem to remain clinically stable and to improve urodynamically when treated with alfuzosin for a long period of time.
Gemcitabine plus Cisplatin in Adjuvant Regimen for Bladder Cancer
Authors: Meliani Enrico , Lapini Alberto , Serni Sergio , Corvino Cristoforo , Carini Marco
Published: July 2003

Objective: To evaluate the toxicity of gemcitabine and cisplatin combination therapy in adjuvant regimen after radical cystectomy for muscle invasive bladder cancer. Patients and Methods: Forty patients underwent radical cystectomy for pT2b–pT4 N0–N2 transitional cell carcinoma of the urinary bladder. They had not received prior systemic chemotherapy and were scheduled to receive gemcitabine 1,000 mg/m2 on days 1, 8, and 15 and cisplatin 70 mg/m2 on day 1 of a 28-day cycle, for 4 cycles. All toxicities were evaluated by World Health Organization toxicity criteria. Results: No toxic deaths occurred. All patients experienced transitory alopecia. 12/40 (30%) patients did not experience any toxicity except for alopecia. 23/40 (57.5%) had hematologic toxicity; 1/40 (2.5%) thrombocytopenia grade 4, and 3/40 (7.5%) granulocytopenia grade 3. All nonhematologic toxicities (21/40, 52.5%), including neurotoxicity, constipation and diarrhea, nausea and vomiting were less than grade 3. Conclusions: Gemcitabine plus cisplatin is a well-tolerated combination therapy with a good clinical safety profile, ethically justifiable in adjuvant regimen for bladder cancer.
Long-Term Results of Transvaginal Colposuspension for the Treatment of Genuine Stress Incontinence Combined with Vaginal Hysterectomy
Authors: Athanasopoulos A. , Barlas P. , Perimenis P. , Dimitrakopoulos S. , Markou S. , Gianitsas K. , Gyftopoulos K. , Hatzipapas J. , Barbalias G.
Published: July 2003

We assessed the long-term efficacy of a modified transvaginal needle bladder neck suspension, combined with vaginal hysterectomy, for the treatment of female stress incontinence. Thirty-two women who underwent this procedure were followed up clinically and urodynamically 1 and 5 years postoperatively. A total of 27 women (84.4%) were cured 1 year postoperatively. Of the 29 women who were followed up 5 years postoperatively, 21 (72.4%) had a satisfactory result (p = 0.157). No significant differences were observed in maximum urine flow rate, residual volume of urine, and functional length of the urethra. On the contrary, the maximum urethral closure pressure was significantly decreased (p = 0.004). Although the results of our study show a decline in success rate by time, the overall long-term efficacy of this technique is undoubtedly satisfactory. This technique is promising as an easy and minimally invasive surgical procedure for bladder neck suspension.
An Alternative Method of Tension-Free Vaginal Tape Implantation for the Treatment of Female Urinary Incontinence
Authors: Tong Yat-Ching
Published: July 2003

Aim: To present an alternative technique of implanting the tension-free vaginal tape (TVT) to minimize the risk of bladder perforation or major pelvic injuries. Patients and Methods: Sixteen female patients with stress urinary incontinence were operated on. The procedure was performed under epidural/spinal anesthesia. A vaginal inverted U incision was made. Dissection was performed alongside the urethra bilaterally and the index finger bluntly dissected into the Retzius space after perforation of the endopelvic fascia. The TVT needle was passed through the lower abdominal wall guided by finger. The rest of the procedure was then finished up as originally described. Results: All patients underwent the operation smoothly without any bladder perforation or major pelvic injury. The mean operative time was 49 (range 32–87) min, and no patient had blood loss >100 ml. All patients could void satisfactorily within 2 weeks. Postoperatively, 94% of the patients (15/16) reported complete dryness, and 6% (1/16) significantly improved. At follow-up after 6 months, the dry rate was 87% (14/16) and the improvement rate 13% (2/16). The 24-hour pad test was significantly improved: preoperatively 112 ± 43 g; postoperatively 8.5 ± 4 g (p < 0.001). The maximum flow rate was not significantly reduced: preoperatively 27.1 ± 8.9 ml/s, postoperatively 24.6 ± 6.4 ml/s (p > 0.05). No patient had residual urine >50 ml. Conclusions: The reported technique offers an alternative way for TVT implantation. The intent is to minimize the risk of major pelvic injury and bladder perforation without compromising the surgical outcomes. Such benefit may outweigh the additional trouble of periurethral dissection.
Does Interstitial Cystitis Urine Include Possible Factors Effecting the Nociceptive System of the Spinal Cord?
Authors: Baykara Mehmet , Erdoğru Tibet , Gülkesen Kemal Hakan , Sargın Canan Figen , Savaş Murat , Ateş Mutlu
Published: July 2003

Introduction: We investigated the effect of interstitial cystitis (IC) urine on bladder layers and nociceptive centers in the spinal cord with determination of nerve growth factor (NGF), neuronal nitric oxide synthase (nNOS) and c-fos expressions. Material and Methods: Female rats were instilled into the bladder IC urine (Group-IC), normal urine (Group-NU) and saline (Group-S). NGF, nNOS and c-fos activity were determined in the L6–S1 medulla spinalis with identification of mast cell and NGF activity on bladder layers. Results: There was more NGF expression cell density in the bladder wall that was determined immunohistochemically in control and IC urine instillation groups than Group-S. While there was no difference in nNOS, NGF and c-fos activity between spinal cord regions except the lateral dorsal horn of the L6 section, localization of activities was different in Group-IC. Conclusions: The characteristics of the bladder wall and its nociceptive afferents after human urine instillation of some toxic compounds might be causative factors for IC. However, it is barely hard to conclude that different toxic compounds should be causative factors in IC urine in the pathogenesis of IC.
Serum Inhibin B Levels Reflect Contralateral Testicular Damage following Unilateral Testicular Trauma
Authors: Özkan Keramettin Uğur , Kücükaydın Mustafa , Muhtaroğlu Sabahattin , Kontaş Olgun , Karaca Fahri
Published: July 2003

Introduction: The aim of this study was to evaluate contralateral testicular damage (CTD) following unilateral blunt testicular trauma (BTT) and testicular capsule laceration (TCL) by the serum inhibin B level which is an accepted marker of spermatogenesis. Methods: Fifty peripubertal male Wistar albino rats were divided into 5 groups each containing 10 rats. Group 1 was the control group. Group 2 was the BTT group in which the right testicle was placed on a firm surface and a metal rod weighing 215 g was dropped onto the testicle from a height of 5.5 cm. Group 3 was the TCL group in which right testicular tunica albuginea was lacerated using the needle of 4/0 silk suture. Group 4 had right orchiectomy initially. Group 5 was the sham group. In all groups, 3-ml blood samples were taken and bilateral orchiectomies were performed 6 weeks after initial manipulations. Results: Groups 2 and 3 had decreased inhibin B levels (p < 0.001), although the orchiectomy group had normal levels. Histological analyses showed lower Johnsen scores for both trauma groups in the ipsilateral and contralateral testes (p < 0.05). Conclusions: Serum inhibin B levels decrease following unilateral testicular trauma reflecting CTD.
Orchidopexy or Orchidectomy for Preventing Tissue Hypoxia in Contralateral Testis following Induction of Ipsilateral Abdominal Testis Associated with Vas deferens Obstruction
Authors: Otçu Selçuk , Karnak İbrahim , Kılınç Asuman , Kılınç Kamer , Tanyel F. Cahit
Published: July 2003

Introduction: An experimental study was planned to evaluate and compare the effects of orchidopexy and orchidectomy on ipsilateral and contralateral testes in rats subjected to ipsilateral abdominal testis and vas deferens obstruction. Materials and Methods: Four groups of 12 rats each were established. Sham operation, intra-abdominal testis with vas deferens obstruction and orchidopexy or orchidectomy for prior intra-abdominal testis with vas deferens obstruction were performed in groups 1, 2, 3 and 4, respectively. While testes were maintained for 8 weeks in the same position in groups 1 and 2, orchidopexy or orchidectomy was performed in groups 3 and 4 after the first 4 weeks, and the remaining testes were harvested after an additional 4 weeks. Lactic acid hypoxanthine contents were determined and the groups were compared with the paired t test. Results: Maintaining intra-abdominal testis with vas deferens obstruction for 8 weeks and orchidopexy yielded the highest lactate values. However lactate levels in contralateral testes did not increase. On the other hand, hypoxanthine levels revealed the highest values after the initial 4 weeks. The 8-week study period resulted in increases of ipsilateral and contralateral testicular hypoxanthine levels. Orchidopexy caused a decrease in ipsilateral testicular values and ameliorated the increase in hypoxanthine levels in contralateral testes. Conclusions: Replacing an intra-abdominal testis with its vas deferens ligated into the scrotum ameliorates the oxidative stress in both ipsilateral and contralateral testes. Since orchidectomy does not result in better contralateral testicular values, orchidopexy should be preferred when treating an undescended testis with vasal obstruction.
Snap-Gauge Band Compared to RigiScan Plus in a Nocturnal Penile Tumescence Study for Evaluation of Erectile Dysfunction
Authors: Mizuno Ichiro , Fuse Hideki , Fujiuchi Yasuyoshi
Published: July 2003

Objective: The aim of this prospective study was to examine the ability of the Snap-Gauge band to differentiate organic from psychogenic erectile dysfunction (ED). Patients and Methods: Nocturnal penile tumescence testing was performed on 12 patients using a Snap-Gauge band and RigiScan Plus. A total of 29 nightly examinations were evaluated. The results obtained with the two methods were compared. Results: The average tumescence, average rigidity, tumescence activity units and rigidity activity units in the positive group (the group of cases in which one, two or three films of the Snap-Gauge band were broken) were each significantly greater than that in the negative group (the group of cases in which no film was broken). The Snap-Gauge band correctly diagnosed 90% of the patients with a sensitivity of 100% and specificity of 75% with respect to results obtained using the RigiScan Plus. Conclusions: The Snap-Gauge band is inexpensive compared to the RigiScan Plus and is relatively reliable. We conclude that the Snap-Gauge band can play a role in ED assessment and can function as a screening device in evaluation of ED.
Bladder Explosion during Transurethral Resection of the Prostate
Authors: Di Tonno Fulvio , Fusaro Valentino , Bertoldin Roberto , Lavelli Dino
Published: July 2003

A case of bladder explosion with wide rupture during transurethral resection of the prostate (TURP) is reported. Immediate cystography was performed and the patient was promptly operated; the postoperative course was uneventful. Intravesical explosion is caused by explosive gas formation and the more dangerous combination is the mixture of air and hydrogen; therefore, the introduction of air during TURP is necessary in order to produce a bladder explosion. This unusual complication of a common urological procedure is rare but serious, and should it arise always requires immediate surgical correction.
Amoxicillin-Induced Nephritis and Tubulitis in a Child
Authors: Ferrara Pietro , D’Aleo Carmen M. , Rigante Donato , Paolini Paoletti Fabrizia , Zannoni Gianfranco , Venuti Laura , Fundarò Carlo , Rendeli Claudia , Salvaggio Elio
Published: July 2003

The occurrence of interstitial nephritis in patients receiving antimicrobial therapy has frequently been reported in adults while it has rarely been described in children. We report the case of a patient treated with amoxicillin who presented hallucinations and serosanguineous blisters during treatment and developed renal failure a few days after discontinuation of the drug. On renal biopsy an interstitial nephritis with tubulitis was identified.
Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow
Authors: De Ugarte Daniel A. , Morizono Kouki , Elbarbary Amir , Alfonso Zeni , Zuk Patricia A. , Zhu Min , Dragoo Jason L. , Ashjian Peter , Thomas Bert , Benhaim Prosper , Chen Irvin , Fraser John , Hedrick Marc H.
Published: July 2003

Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.
Generation and Characterization of Multicellular Heterospheroids Formed by Human Peripheral Blood Mononuclear Cells
Authors: Seitzer Ulrike , Gerdes Johannes
Published: July 2003

A three-dimensional culture system for primary human mononuclear cells was developed, which reproducibly resulted in the formation of multicellular heterospheroids. Immunohistological characterization demonstrated not only the three-dimensional tissue-like aggregation of primary monocytes, B cells and T cells, but also the presence of macrophages and proliferating cells, indicating that a differentiation of monocytes to macrophages and an activation of cells were induced. Because of the phenotypical resemblance to granulomas the influence of an in vitro infection with mycobacteria on spheroid formation and morphology was analyzed. In comparison to control incubations, the formation of multinucleated giant cells and necrotic areas containing large numbers of mycobacteria could be observed, which resembled histological hallmarks of in situ tuberculoid granulomas. These characteristics have not been described for in vitro models of granuloma formation before and thus this new culture technique may prove to be a useful tool for analyzing aspects relevant to immunopathological processes in chronically inflamed tissues.
Impact of Overall Treatment Time on Local Control of Anal Cancer Treated with Radiochemotherapy
Authors: Graf R. , Wust P. , Hildebrandt B. , Gögler H. , Ullrich R. , Herrmann R. , Riess H. , Felix R.
Published: July 2003

Between 1987 and 2000, 111 patients with epidermoid anal cancer (T1–T4 Nx M0) were assigned to primary simultaneous radiochemotherapy (RCT) with a radiation dose of 45 Gy, performed either as a split course with 2-Gy single fractions (schedule A, 1987–1996, n = 65 patients) or continuously with fractions of 1.8 Gy (schedule B, 1996–2000; n = 38 patients). The chemotherapy consisted of continuous infusions of 5-fluorouracil (5-FU; 800/1,000 mg/m2/day, on 4/5 consecutive days, during weeks 1 and 5) together with one (schedule A) or two (schedule B) short infusions of mitomycin C (10 mg/m2) during the first course of 5-FU. Associations between clinical outcome and various prognostic factors were assessed in 103 patients who completed these schedules. For both patient groups combined, 5-year local control rate was 67% and 5-year survival rate 71%. Advanced tumor stage, size, and nodal status significantly decreased the 5-year local control rate as well as the overall treatment time (OTT) >41 days (58% for OTT >41 days vs. 79% for OTT ≤41 days; p = 0.04). However, we did not find a correlation with the prescribed radiotherapy schedule (A or B). In conclusion, in patients with anal carcinomas treated with RCT with a radiation dose of 45 Gy, the predominant determinant of local control is the resulting OTT and not the administration schedule (split course or continuous radiotherapy).
Pain after Quadrantectomy and Radiotherapy for Early-Stage Breast Cancer: Incidence, Characteristics and Influence on Quality of Life
Authors: Amichetti Maurizio , Caffo Orazio
Published: July 2003

Purpose: Conservative breast surgery (CBS) is viewed as a surgical technique able to improve the psychophysical outcome of women who underwent surgery for breast cancer (BC). CBS has clearly improved the impact of local treatment on postoperative body image adjustment, but the effect on patients’ quality of life (QL) is similar to that observed after mastectomy. This insufficient adjustment may be related to the fact that sensorial alterations, mainly pain, may produce negative effects on patients’ QL. This retrospective study, based on self-completed questionnaires, reports the patients’ descriptions of pain and its relationships with QL adjustment after quadrantectomy and radiotherapy for BC. Patients and Methods: We mailed a questionnaire to a consecutive series of 481 patients treated with CBS and radiotherapy from March 1995 to March 1998. The questionnaire, listing 129 items, comprised: (1) a pain assessment module with the short form of the McGill Pain Questionnaire exploring the characteristics and the description of the pain; (2) a QL questionnaire including four subscales (physical well-being, psychological well-being, physical autonomy, and relationships). Results: Three hundred and forty-eight patients (72%) completed the questionnaire, but 24 were excluded from the analysis due to absence of axillary dissection. One hundred and forty-one patients reported pain as a consequence of treatment. It generally started within 3 months after the completion of therapy, was localized in the axillary region and was intermittent. The pain was mainly described as aching (59%), tender (51%) and cramping (43%). Compared to the patients who did not experience pain, those who suffered from pain had significantly worse scores in physical (p < 0.0001), psychological (p < 0.0001), autonomy (p < 0.05), and relational subscales (p < 0.0001). Conclusions: Our data support the hypothesis that pain is a frequent sequela of CBS and radiotherapy, and that such symptoms can cause postoperative psychosocial distress, thus limiting patient adaptation and reducing the beneficial effect of CBS on body image.
Increased Expression of RelA/Nuclear Factor-κB Protein Correlates with Colorectal Tumorigenesis
Authors: Yu Hong-Gang , Yu Liang-Liang , Yang Yanning , Luo He-Sheng , Yu Jie-Ping , Meier Juris J. , Schrader Henning , Bastian Andreas , Schmidt Wolfgang E. , Schmitz Frank
Published: July 2003

Objective: To identify the role of RelA/nuclear factor-ĸB, an important inhibitor of apoptosis in colorectal tumorigenesis, we examined the expression of RelA in normal colorectal mucosa (n = 10), colorectal adenomas (n = 30) and colorectal adenocarcinomas (n = 30). Furthermore, the association of RelA expression with tumor cell apoptosis, proliferation, and expression of Bcl-2/Bcl-xL was also studied. Methods: Paraffin sections were stained with monoclonal antibodies directed against RelA, Bcl-2, Bcl-xL, and Ki-67 to assess protein expression patterns in normal, adenomatous and colon cancer tissue. Apoptotic cells were detected by terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) using an in situ detection kit. Results: The results of immunohistochemical staining revealed that expression of RelA, Bcl-2, Bcl-xL, and Ki-67 labeling index (LI) significantly increased in the transition from adenoma with low dysplasia to adenocarcinoma. This transition was associated with a significant decrease in the apoptotic index (AI) and a significant increase in the Ki-67 LI. The expression of RelA correlated inversely with the AI and correlated positively with the expression of Bcl-2, Bcl-xL, and Ki-67 LI in the transition from low-grade dysplasia to adenocarcinoma. Conclusion: Our results suggest that increased expression of RelA/nuclear factor-ĸB plays an important role in the transition from colorectal adenoma with low-grade dysplasia to adenocarcinoma in the pathogenesis of colon cancer in humans.
A Novel Case of a CAT to AAT Transversion in Codon 179 of the p53 Gene in a Supratentorial Primitive Neuroectodermal Tumor Harbored by a Young Girl
Authors: Postovsky Sergey , Ben Arush Myriam Weyl , Elhasid Ronit , Davidson Sima , Leshanski Lucy , Vlodavsky Eugene , Guilburd Joseph N. , Amikam Dorit
Published: July 2003

Background: The most common cytogenetic abnormality encountered in primitive neuroectodermal tumors (PNET)/medulloblastoma is loss of heterozygosity in the region of the short arm of chromosome 17. There is some evidence that supratentorial PNET has different cytogenetic markers than infratentorial PNET/medulloblastoma. Particularly, loss of 17p is more frequent in the latter than in the former. We describe a young girl diagnosed with supratentorial PNET (SPNET). Analysis of the tumor suppressor gene p53 in the tumorous tissue revealed a rare transversion mutational event of CAT to AAT in position 179 of exon 5. To the best of our knowledge, this is the first case of such a transversion at codon 179 in the p53 gene in SPNET. Case Report: A 12-year-old girl was admitted with nausea, headache and vision disturbances. MRI of the brain showed a large space- occupying lesion in the right frontal lobe. Histological examination of the macroscopic resection of the tumor revealed PNET of the brain. Polymerase chain reaction-single strand conformation polymorphism analysis of all p53 exons was performed, and a unique variant of a transversion at codon 179 of exon 5 was revealed. Therapy was started according to the Children’s Cancer group protocol (CCG-99702) designated for treatment of high-risk central nervous system embryonal tumors. She received an initial course of chemotherapy, consisting of cyclophosphamide and vincristine for mobilizing and harvesting peripheral blood stem cells (PBSCs). Then she was given craniospinal irradiation (3,600 cGy) with a boost to the tumor bed (1,980 cGy) and three consecutive courses of high-dose chemotherapy with carboplatin, vincristine and thiotepa/cyclophosphamide, with PBSCs support after each course. Results: The patient is in complete remission 17 months after diagnosis, based on the results of physical examination and imaging studies. Discussion: The mutation results in an alteration of the amino acid HIS to ASN. The amino acids surrounding position 175 play an important role in stabilizing the p53/DNA complex. There are only 12 known mutations of the reported type, and the finding of such a rare mutational event in a low-incidence p53 mutation tumor, such as SPNET, might add additional insight into the p53-SPNET relationship in tumorigenesis. Although not widely accepted, it is possible that different mutations of the p53 gene in patients with brain tumors may imply a different ultimate prognosis. In our case, we cannot exclude the fact that transversion of CAT to AAT in position 179 of exon 5 may explain prolonged survival of a patient with good response to therapy.
Prognostic Role of Serum Sialyl Lewisx (CD15s) in Colorectal Cancer
Authors: Paganuzzi Michela , Bobbio Barbara , Marroni Paola , Filiberti Rosa , Secco Giovanni Battista , Grossi Carlo Enrico
Published: July 2003

Objective: Sialyl Lewisx (sLex) is one ligand for E selectin (CD62E), a glycoprotein that is expressed on activated endothelial cells. Adhesion mediated by endothelial E selectin and sLex expressed on human tumor cells could be relevant for the development of metastases. The aim of this study was to investigate whether or not a correlation exists between pre-operative levels of ganglioside serum sLex and disease-free interval and survival in colorectal cancer patients. Patients and Methods: Thirty Duke’s B and 52 Duke’s C patients undergoing resection for colorectal cancer were studied. The median follow-up time was 34.8 months. A pool of 57 sera from normal subjects was used as an Internal Normal Standard (INS). sLex analyses were performed by a thin layer chromatography (TLC) immunostaining technique. Results were expressed as the ratio (R) between bands of INS and bands from each neoplastic serum. Results: The median R value was 0.80 in normal subjects, 0.70 in Duke’s B patients and 1.0 in Duke’s C patients. No significant differences were detected between sLex concentrations in sera from normal and neoplastic subjects (p = 0.1). Using an arbitrary cutoff of R = 0.9, the mean disease-free interval in the whole series was 47.4 months for R <0.9 and 126.0 months for R ≧ 0.9 (p = 0.04). The survival time was 76.8 months for patients with R values <0.9 and 156.3 months for patients with R values ≧0.9 (p = 0.1). Conclusions: High serum levels of ganglioside sLex significantly correlate with a favorable prognosis and with a lower occurrence of metastases. It is conceivable that soluble sLex may compete with membrane-bound sLex in the course of interactions between activated endothelium and tumor cells that have reached the circulation.
Molecular Biologic Characteristics of Seven New Cell Lines of Squamous Cell Carcinomas of the Head and Neck and Comparison to Fresh Tumor Tissue
Authors: Welkoborsky Hans-J. , Jacob Roland , Riazimand Seyed H. , Bernauer Hubert S. , Mann Wolf J.
Published: July 2003

Background: Squamous cell carcinoma (SCC) is the most frequent malignant tumor of the upper aerodigestive tract. Cell lines of these tumors facilitate the investigation of various tumor biological parameters. This study was conducted to compare molecular biologic characteristics between cell lines and fresh tumor tissue. Methods: In seven SCC-derived cell lines, cytokeratin 5/6 and cytokeratin 19 expression, DNA content, chromosome aberrations and tumorigenicity were assessed in nude rats. Unbalanced numerical and structural chromosomal aberrations were investigated by comparative genomic hybridization (CGH), and results were compared to those obtained in fresh tumor tissues of the same patients. Results: All cell lines expressed cytokeratins 5/6 and 19, indicating their epidermoid origin. Tumor growth after transplantation into nude rats occurred in five of seven cell lines. Routine histology and immunohistochemical examinations confirmed SCC. Aneuploidy was detected in all cell lines, with a 2c deviation index ranging from 1.9 through 9.5 and a 5c exceeding rate ranging from 2.6 through 36.7%. The most frequent chromosomal aberrations in cell lines were overrepresentations of chromosomal material on chromosomes 15q, 7p (5 cases each), 3q, 5p (4 cases each), and 11q and 17q (3 cases each) and losses of chromosomal material on chromosomes 3p, 18q (3 cases each), and 19p and 7q (2 cases each). Comparing these results to CGH analysis of fresh tumor tissue from the same patients, overrepresentations of chromosomal material on 10q, 20q and 21q, along with loss of chromosomal material on 4q was detected more frequently in primary tumors, whereas overrepresentations on 7p and loss of chromosomal material on 7q were more frequently detected in cell lines. Nevertheless, there was a high degree of similarity of chromosomal alterations in cell lines and corresponding fresh tumor tissue. Conclusion: The data suggest a high degree of genetic similarity between tumor cells of cell lines and the tumors from which they were derived. Therefore, these cell lines can serve as an accurate model to investigate cell biology of SCC in vitro.
Expression of c-met Tyrosine Kinase Receptor Is Biologically and Prognostically Relevant for Primary Cutaneous Malignant Melanomas
Authors: Cruz João , Reis-Filho Jorge S. , Silva Paula , Lopes José Manuel
Published: July 2003

Objectives: The c-met tyrosine-kinase receptor and its ligand hepatocyte growth factor are involved in cell survival, proliferation, motility, and invasion. Experimental data have suggested a putative role in melanomagenesis and progression of cutaneous malignant melanoma (CMM). We sought to evaluate c-met expression in a cohort of 62 primary CMM patients diagnosed and primarily treated at the same institution. Methods: Sixty-two cases of CMM were retrospectively retrieved from the archives of the Department of Pathology, Hospital São João, Porto, Portugal. All classical clinicopathological features were reviewed. Only those patients in whom representative paraffin blocks were available and the diagnosis of primary CMM was confirmed, and who were followed up after the primary diagnosis were included in the study. Immunohistochemistry for c-met was performed in 59 cases, and semiquantitatively and qualitatively (membranous and cytoplasmic, M+C, or cytoplasmic) evaluated. Statistical analysis was performed using χ2, ANOVA and Kaplan-Meier/log-rank tests. Results: M+C pattern of c-met expression was significantly associated with presence of vertical growth phase (p = 0.0198), thick tumors (p = 0.0006), ulceration (p = 0.0386), high mitotic index (p = 0.0008), lymphatic (p = 0.0086) and vascular (p = 0.0080) invasion, and nodal (p = 0.0422) and combined (nodal and/or visceral) metastases (p = 0.0234). M+C pattern of c-met expression also proved to be a significant prognostic factor for overall survival in univariate analysis (p = 0.0125). Conclusions: Our findings suggest that the pattern of c-met expression is a relevant prognostic factor for overall survival and is associated with more aggressive behavior of primary CMMs.
Abnormal Fragile Histidine Triad Expression in Advanced Cervical Cancer and Evaluation of Its Utility as a Prognostic Factor
Authors: Machida Shizuo , Ohwada Michitaka , Saga Yasushi , Suzuki Mitsuaki
Published: July 2003

Objective: The relationship between the abnormal expression of fragile histidine triad (FHIT) and the prognosis in advanced cervical cancer was investigated, focusing on the relation with radiosensitivity. Methods: A retrospective study was performed in 54 patients with stage IIIb cervical squamous cell carcinoma who received radiation therapy as the initial treatment. Formalin-fixed paraffin-embedded tissues were immunohistochemically stained using anti-FHIT antibody. The survival curve for patients with abnormal FHIT expression (low expression) was prepared and the prognosis was compared with that for the normal expression group. The decrease rate of the serum squamous cell carcinoma antigen (SCC) levels (SCC index = SCC level after radiotherapy/SCC level before radiotherapy) was calculated. Results: Abnormal FHIT expression was observed in 25 patients (46%). There were no significant differences in clinical backgrounds between the abnormal and normal FHIT expression groups. The 5-year survival rate was 72% in the abnormal expression group, showing no significant difference from that in the normal expression group (64%). The SCC indices were 0.21 ± 0.14 and 0.29 ± 0.19 in the abnormal and normal expression groups, respectively, showing no significant difference between the two groups. Conclusions: Abnormal FHIT expression was not correlated with radiosensitivity in patients with stage IIIb cervical cancer, showing that abnormal FHIT expression cannot be used as a prognostic factor.
Functional Endurance Capacity and Exercise Training in Long-Term Treatment after Heart Transplantation
Authors: Tegtbur Uwe , Pethig Klaus , Machold Heike , Haverich Axel , Busse Martin
Published: July 2003

Objective: The aim of this study was to investigate the influence of cardiac denervation on endurance exercise capacity in heart transplant recipients (HTR) in comparison to patients with coronary artery disease (CAD). Methods: We performed two successive incremental tests and a 30-min constant load test (CLT) in 20 HTR (55 ± 7 years old, 4.9 ± 2.2 years after transplantation) and in 13 patients with CAD (58 ± 8 years). Results: Maximal workload in HTR was 106 ± 25 W (163 ± 41 W; p < 0.01). In CLT at anaerobic threshold of 55 ± 6 W (97 ± 34 W; p < 0.01), lactate increased from 0.9 ± 0.2 (1.0 ± 0.2) to 2.9 ± 1.3 (3.3 ± 1.3) after 10 min and to 3.1 ± 1.6 (3.4 ± 1.5; NS) mmol · l–1 after 30 min, confirming that the anaerobic threshold reflects a steady state. The CLT kinetics of heart rate (+6 beats in HTR and in CAD between 10th and 30th min) and lactate are comparable in HTR and CAD, demonstrating that endurance kinetics are not influenced by cardiac denervation.
Dietary Intake of Various Nutrients in Older Patients with Congestive Heart Failure
Authors: Gorelik Oleg , Almoznino-Sarafian Dorit , Feder Ilana , Wachsman Orit , Alon Irena , Litvinjuk Vladimir , Roshovsky Mira , Modai David , Cohen Natan
Published: July 2003

Background and Aims: Anorexia, nausea and premature satiety with eating, prevalent in congestive heart failure (CHF), have been held responsible for reduced dietary intake and deficiency of magnesium, potassium and probably other nutrients. Since solid data is not available, this study was undertaken with the following aims (1) to assess dietary intake in CHF, (2) to compare dietary intake in older CHF patients with a similar patient population free of CHF (control group), and (3) to evaluate these data in patients with moderate versus severe CHF. Methods and Results: Dietary intake of 57 consecutively hospitalized furosemide-treated CHF patients over the age of 60 was compared with that of 40 similar patients free of CHF. In addition, a statistical analysis was performed comparing the data of the 37 patients with moderate versus the 20 patients with severe CHF. Dietary content of various nutrients was assessed with the food frequency recall technique. Dietary intake was comparable in the two respective pairs of groups. However, the intake of magnesium, calcium, zinc, copper, manganese, energy, thiamin, riboflavin, and folate in all subgroups fell short of recommended levels for intake, while vitamins A, C and niacin contents exceeded those recommended. Intakes of potassium andproteins were within the recommended values. Conclusions: CHF per se, even severe CHF, is not responsible for a reduced dietary intake of various nutrients. A population-related dietary culture, old age or other chronic conditions, rather than CHF, might be mainly involved. The increased intake of vitamins A, C and niacin in our patients may be attributed to the high content of fruits and vegetables in the Mediterranean diet. Insufficient intake of the above-mentioned group of electrolytes and essential nutrients may contribute to the frequently observed negative balance of some of them. This is especially relevant in furosemide-treated CHF patients. Therefore, supplementation should be considered.