bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Irradiation for Therapy of Retinoblastoma in Children More Than 1 Year Old: The St. Jude Children's Research Hospital Experience and Review of Literature
Authors: Fontanesi James , Pratt Charles B. , Hustu H. Omar , Coffey Douglas , Kun Larry E. , Meyer David
Published: February 2007

Fifteen children (>1 year old at diagnosis) were treated for retinoblastoma (RB) with primary irradiation at St. Jude Children's Research Hospital between January 1963 and January 1992. Staging of the 19 treated eyes was as follows: Reese‐Ellsworth (R‐E) Groups I and II, n = 7; Group III, n = 3; Group IV, n = 1; Group V, n = 7; information on one globe is incomplete. Total dosage ranged from 25 to 45 Gy (median = 40 Gy) in fractions of 170–225 cGy delivered 5x/week (n = 13) or 225–265 cGy delivered 4x/week (n = 4 eyes) or x5/week (n = 2 eyes). Treatment techniques included anterior field (n = 11) or lens‐sparing technique (n = 8). One patient has died of progressive central nervous system (CNS) disease at 13 months; one patient succumbed to second malignant neoplasm within the irradiated field at 194 months; the remaining 13 patients remain alive from 27 to 301 months (median = 178 months). Local control with irradiation alone has been maintained in 12 eyes. Four eyes with local recurrence were salvaged using cryotherapy or reirradiation. Enucleation was required for three eyes for progressive disease at 4, 7, and 7 months postirradiation. Cataract formation was documented in nine eyes treated with anterior fields and in one patient treated with lens‐sparing technique. At last follow‐up, 7 patients had visual acuity of 20/100 or better. Radiation dose of 40 Gy appears to be adequate for local control of early stage RB (R‐E Groups I‐III and VB whose tumors are R‐E Groups I‐III) in patients >1 year old. The results of this limited series which has lengthy follow‐up is compared with the results of previously published data in an effort to define the benefits and disadvantages of the different treatment techniques which have been reported in the treatment of RB in children >1 year old. © 1995 Wi1ey‐Liss, Inc.
Veno‐occlusive Disease of the Liver After Chemotherapy for Rhabdomyosarcoma: Case Report With a Review of the Literature
Authors: Kanwar Vikramjit S. , Albuquerque Maria Luiza C. , Ribeiro Raul C. , Kauffman William M. , Furman Wayne L.
Published: February 2007

We describe the case of a 3‐year‐old girl who developed veno‐occlusive disease of the liver while receiving chemotherapy for parameningeal rhabdomyosarcoma. After suffering lethargy and oral mucosal bleeding for one day, the patient exhibited a sudden weight gain and refractoriness to platelet transfusions. Symptoms rapidly worsened with elevation of liver enzymes, bleeding diatheses, and respiratory failure. An ultrasound scan of the liver demonstrated reversed flow in the portal vein. Maximal supportive care, including tracheal intubation and mechanical ventilation, was required. The patient gradually recovered with no respiratory and minimal neurological sequelae. Veno‐occlusive disease of the liver should be considered in children receiving chemotherapy who develop weight gain, a sudden drop in platelet count and derangement of liver enzymes. Aggressive supportive measures should be instituted if necessary, as patients surviving the acute phase can expect to make a full recovery. © 1995 Wi1ey‐Liss, Inc.
Cardiac Failure and Dysrhythmias 6–19 Years After Anthracycline Therapy: A Series of 15 Patients
Authors: Steinherz Laurel J. , Steinherz Peter G. , Tan Charlotte
Published: February 2007

The clinical course of late symptomatic anthracycline cardiomyopathy, and resultant changes of cardiac function, were described in 15 patients. They represented a subset of 300 patients who had cardiac evaluations to identify the prevalence of late cardiotoxicity more than 4 years after anthracycline therapy in these patients. The clinical course and all available cardiac evaluations including electrocardiography, continuous taped electrocardiography, echocardiography, radionuclide cardiac angiography, cardiac catheterization, and endomyocardial biopsy, of the 15 patients were reviewed. The patients had received 285–870 (median 540) mg/M2 of daunorubicin and/or doxorubicin 6–19 (median 12) years prior to the onset of late symptoms. Seven patients also had 2,100–4,000 cGy mediastinal radiotherapy. Five patients had required treatment for cardiac symptoms at the end of chemotherapy but 10 patients had no cardiac problems anteceding their late decompensation. Fractional shortening on echocardiogram at late decompensation was 8–20% (median 17%) and radionuclide left ventricular ejection fraction was 8–59% (median 38%). All were treated with digitalis and diuretics and 13/15 with afterload reduction, with at least transient improvement of symptoms. They were followed for 1–9 (median 3) years after late decompensation. One died of uncontrollable cardiac failure. Another underwent successful cardiac transplantation. Conduction abnormalities and dysrhythmias were present in 14/15 patients and 3 died suddenly. Two more had syncope, one requiring an automatic cardiac defibrillator. Endomyocardial biopsy or autopsy revealed hypertrophy and fibrosis in 10/10 patients. Our patients with early cardiac symptoms improved transiently but decompensated later and patients with no early symptoms developed cardiac symptoms more than 10 years after anthracycline therapy. Therefore, patients who have received anthracyclines should have continued cardiac evaluation. © 1995 Wi1ey‐Liss, Inc.
Safety and Efficacy of I‐Leucovorin Rescue Following High‐Dose Methotrexate for Osteosarcoma
Authors: Goorin Allen , Strother Douglas , Poplack David , Letvak Laurie A. , George Martine , Link Michael
Published: February 2007

High‐dose methotrexate with leucovorin rescue (HDMTX‐LCV) is an important component of regimens used in the treatment of osteosarcoma. As of this writing the commercially available form of leucovorin is a racemic mixture of d‐ and l‐diastereoisomers; the l‐isomer is the active component. This study describes the efficacy and safety of l‐leucovorin in HDMTX‐LCV regimens. Fifteen patients with osteosarcoma who were enrolled into or treated according to Pediatric Oncology Group protocols 8759 and 8651 received l‐leucovorin (7.5 mg every 6 hours) in place of d,l‐leucovorin following high‐dose methotrexate. Safety data were collected for 1 week after each course or until any toxicities resolved. The mean number of l‐leucovorin doses per course was 16.2 and the mean total dose per course was 126 mg. Adverse experiences were generally mild or moderate and occurred in 54 (60%) of 90 courses of l‐leucovorin therapy. One l‐leucovorin patient, who had inadequate methotrexate rescue, developed severe typhlitis. There were no instances of severe, acute methotrexate toxicity. Myelosuppression was seen but, in general, was not severe. These results support the conclusion that l‐leucovorin effectively rescues patients from the toxicity of high‐dose methotrexate. © 1995 Wi1ey‐Liss, Inc.
Malignant histiocytosis: A reassessment of cases formerly classified as histiocytic neoplasms and review of the literature
Authors: Egeler R. Maarten , Schmitz Laura , Sonneveld Pieter , Mannival Carlos , Nesbit Mark E.
Published: February 2007

Malignant histiocytosis (MH) and true histiocytic lymphoma (THL) are hematopoietic malignancies of the mononuclear phagocytic system distinguished from each other by clinical presentation and presumed cell of origin. THL present as a localized mass derived from the fixed tissue histiocyte which may or may not disseminate. MH originates from the circulating monocyte or tissue macrophage and is characterized by a syndrome of systemic symptoms, pancytopenia, adenopathy, hepatosplenomegaly, and wasting. The distinction between MH and THL is at times arbitrary and overlap exists between these syndromes. The clinicopathologic studies that defined these entities were performed prior to the development of immunophenotyping and other molecular techniques currently used to ensure proper classification of hematopoietic malignancies. Nine patients from the University of Minnesota originally diagnosed with MH were retrospectively analyzed using a panel of antibodies reactive against T cell, B cell, and myelomonocytic antigens. Only one patient was reclassified as a possible histiocytic malignancy after reevaluation. Similar immunophenotyping studies have also shown cases previously diagnosed as MH or THL express lymphoid antigens, and would now be classified as Ki‐1 positive anaplastic large cell lymphoma (ALCL) or some other hematopoietic neoplasm. These results indicate true histiocytic neoplasms are extremely rare, and previous concepts concerning clinical presentation and therapeutic outcome of the entities are inaccurate. In this paper we summarize the results of multiple retrospective analyses of cases previously diagnosed as MH or THL, including our experience at University of Minnesota, to illustrate the overall rarity of these entities. The current literature on malignant histiocytic disorders is reviewed, and the clinical presentation of patients determined to have histiocytic malignancies using contemporary analytical techniques is discussed. © 1995 Wiley‐Liss, Inc.
Cyclosporine therapy for refractory langerhans cell histiocytosis
Authors: Aricò Maurizio , Colella Roberto , Conter Valentino , Indolfi Paolo , Pession Andrea , Santoro Nico , Burgio G. Roberto
Published: February 2007

Optimal treatment for Langerhans Cell Histiocytosis (LCH) has not yet been established. Preliminary reports suggest some effect of cyclosporine (CSA), both alone or in combination with steroids and/or vinblastine, in untreated cases. Twelve children (6 females and 6 males, age at diagnosis 3 months to 4 years) with biopsy proven, systemic LCH received oral CSA (12 mg/kg/day in two divided doses given daily) as a second‐line therapy following chemotherapy including vinblastine and/or etoposide (10 cases) or steroid alone (one case); one child was not pretreated. A total of 16 CSA courses were administered to the 12 patients: 8 were completed, 4 were interrupted as unsuccessful, and 4 are still ongoing. CSA related toxicity consisted of hypertrichosis and transient hypertension and was never limiting. Treatment was associated with a clinical response in 8/12 patients: 3 had a complete response and are off therapy, and 5 had a partial response; disease reactivation following first favorable response required additional CSA courses in 3 patients. Four patients failed to respond to CSA: two died of progressive disease, while two had a favorable response to CSA + VP16. Favorable response to CSA was not related to CSA trough and peak levels and was usually observed during the first 2 weeks of CSA therapy.

CSA is effective for treatment of LCH also in pretreated children with progressive disease including life‐threatening organ dysfunction. Long‐lasting complete remission may be achieved after 6 to 12 months of CSA therapy. When disease reactivation occurs after treatment withdrawal, a second course may be followed by favorable response. As minimal or no adverse effects are observed during or after prolonged CSA therapy, this may also be safely used in young patients.
Significance of lymphoblasts in cerebrospinal fluid in newly diagnosed pediatric acute lymphoblastic malignancies with bone marrow involvement: Possible benefit of dexamethasone
Authors: van den Berg Henk , Vet Raymond , den Ouden Emmy , Behrendt Henk
Published: February 2007

We analyzed retrospectively the data on 135 children treated since 1983 for acute lymphoblastic leukaemia and non‐Hodgkin's lymphoma with bone marrow involvement with respect to the presence of lymphoblasts in cerebrospinal fluid (CSF) and the number of cells in CSF, both at initial diagnosis and during follow‐up. Of these children 96, 11, and 28 suffered from B‐progenitor, mature B‐cell, and T‐cell malignancies, respectively. In two patients initial central nervous system involvement was documented by the presence of lymphoblasts with high CSF cell counts (B+C+ patients); 19 patients had CSF lymphoblasts with normal CSF cell counts (B+C− patients); the others had no CSF blasts and normal CSF cell counts (B‐C‐ patients). In B+C− and B‐C‐ patients 5‐year‐leukaemia‐free survival was 66 and 70%, respectively (i.e., not significantly different). None of the B+C− patients experienced a first relapse in the central nervous system. Differences in outcome by comparing with reports of others may be related to the use of dexamethasone instead of prednisone in almost all of our patients. © 1995 Wiley‐Liss, Inc.
Anaplastic renal cell carcinoma following neuroblastoma
Authors: Krigman Hannah R. , Bentley Rex C. , Strickland Donald K. , Miller Cindy R. , Dehner Louis P. , Washington Kay
Published: February 2007

Renal cell carcinoma is unusual in children. We report a case of anaplastic renal cell carcinoma arising in a 7‐year‐old girl following treatment for Stage III neuroblastoma. The renal cell carcinoma has unusual histologic and ultrastructural features, which are discussed. The case is further unusual in that few children with advanced stage neuroblastoma survive long enough to develop second malignant neoplasms. © 1995 Wiley‐Liss, Inc.
Transient myeloproliferative disorder associated with trisomy 21, a wide range syndrome: Report of two cases with trisomy 21 mosaicism
Authors: Zubizarreta Pedro , Muriel Federico Sackmann , Barbieri María Angélica Fernández
Published: February 2007

Transient myeloproliferative disorder (TMD) is an uncommon syndrome strongly associated with abnormalities of chromosome 21. Blast transient proliferation appears most frequently at neonatal age and usually resolves spontaneously in two or three months.

Two patients, a girl and a boy, with neonatal onset of TMD are reported. They both presented trisomy 21 mosaicism according to bone marrow cytogenetic analysis. Patient 1, on one end of the spectrum, showed a “classic” benign course with rapid resolution and favorable outcome. Patient 2, on the other hand, had two blast outbursts both followed by spontaneous remissions. He failed to thrive and never reached a good general condition, dying at 5 months of age from a respiratory infectious complication. The necropsy showed generalized extramedullary hemopoiesis without evidence of bone marrow blast infiltration or myelofibrosis.

TMD has some clinical and laboratory features that make it unique and distinguishable from true congenital leukemia with which it may be initially mistaken. It usually has a benign course followed by a favorable outcome.

As trisomy 21 mosaicism may not have overt phenotypic stigmata, it is possible that many cases of TMD in these children may have a silent, non‐detected course.

We also conclude that a favorable outcome is not always to be expected in TMD. © 1995 Wiley‐Liss, Inc.
Dental abnormalities in long‐term survivors of head and neck rhabdomyosarcoma
Authors: Kaste Sue C. , Hopkins Kenneth P. , Bowman Laura C.
Published: February 2007

To define the long‐term dental sequelae of therapy for childhood rhabdomyosarcoma of the head and neck, and to identify factors in their development, we retrospectively reviewed the serial panoramic radiographs and clinical records of 22 survivors of head or neck rhabdomyosarcoma who had been followed for at least 5 years. Patients were divided into four groups based upon age at the time of therapy and three groups based upon radiation doses. All patients had received similar multiagent chemotherapy. Dental sequelae of oncotherapy occurred in over half of the long‐term survivors of head and neck rhabdomyosarcoma. The abnormalities comprised root stunting in 54%, microdontia in 23%, and hypodontia in 50% of patients; 36% had multiple abnormalities. Microdontia and multiple abnormalities were more prevalent in patients treated at the earliest age, and abnormalities tended to be more prevalent with increasing doses of radiation. Five patients (23%) developed severe cosmetic and/or functional sequelae necessitating surgical and/or orthodontic intervention. The high frequency of dental sequelae we observed suggests that meticulous long‐term dental and radiographic follow‐up are needed. Early detection and treatment of the complications of therapy will expedite their correction and minimize morbidity. © 1995 Wiley‐Liss, Inc.
Acquired von willebrand disease in malignant peripheral neuroectodermal tumor (PNET)
Authors: Nowak‐Göttl U. , Kehrel B. , Budde U. , Hoffmann C. , Winkelmann W. , Jürgens H.
Published: February 2007

In week 12 of the EICESS 92 protocol a 12‐year‐old boy with pelvic PNET developed acquired von Willebrand disease: bleeding time was prolonged (<15 min) and von Willebrand factor antigen (54%) and ristocetin cofactor activity (50) were reduced. Platelet aggregations with thrombin and collagen and the number of major platelet glycoproteins/per platelet did not differ from the controls. After Haemate P® (Behring Werke, Marburg, Germany) bleeding time normalized and surgery could be performed without occurrence of bleeding episodes. Three weeks after surgery bleeding time, ristocetin cofactor activity, and von Willebrand factor antigen increased to normal paediatric values. Without occurrence of further bleeding episodes the patient received another 10 courses of polychemotherapy (EICESS 92).
Acute limb ischemia due to malignant arterial embolism from a metastatic germ cell tumor
Authors: Stein Moshe E. , Drumea Keren , Ben‐Itshak Ofer , Hoffman Aharon , Eyal Abraham , Moshkovitz Boaz , Haim Nissim
Published: February 2007

Arterial tumor embolization is a rare but serious complication of neoplastic disease. The majority of these tumors are associated with primary or secondary lung malignancies, originating from pulmonary vein metastasis or from an atrial mass. Malignant germ cell tumors primarily disseminate to the retroperitoneal lymph nodes and lung, and to the brain and liver later in the course of the disease. A germ cell tumor metastasis embolizing to the iliac‐femoral arterial system has not yet been reported. We report a metastatic embolism in a patient with disseminated embryonal cell carcinoma causing acute limb ischemia, managed by surgical embolectomy. The sudden development of limb ischemia in a patient with a germ cell tumor should alert the physician to the possibility of tumor embolism. © 1995 Wiley‐Liss, Inc.
Childhood acute lymphoblastic leukemia in India: An approach to managementin a three‐tier society
Authors: Chandy Mammen
Published: February 2007

Within a population of 882 million, six thousand children will develop acute lymphoblastic leukemia each year in India. These children come from three socio‐economic backgrounds: Profile I (70%) being extremely poor who cannot afford any treatment unless it is provided free, Profile II (25%) from the middle class, and Profile III (5%) who can afford to have the best possible treatment. Current protocols for childhood ALL range from simple low‐cost regimes like UKALL VIII, intermediate intensity regimes like BFM 76/79, and aggressive regimes aimed at increasing cure rates in the high risk groups. Since state resources are limited, the pediatric oncologist in India has to decide on the appropriate treatment protocol for the individual child in each of these profiles. This paper suggests an approach to managing childhood ALL in developing countries like India. © 1995 Wiley‐Liss, Inc.
Hodgkin's disease in children: A retrospective study of the 20‐year experience (1968–1987) at a single institute
Authors: Kolygin Boris A.
Published: February 2007

Between 1968 and 1987, 356 previously untreated consecutive children with Hodgkin's disease (HD), aged under 14, were treated at the Pediatric Department of N.N. Petrov Research Institute of Oncology (St. Petersburg, Russia). Prevailing among histologic subtypes were lymphocytic predominance and mixed cellularity (34 and 31.7%, respectively). Two‐thirds of the patients (67.7%) were with Stages III‐IV and one‐third (32.3%) with Stages I‐II.

Radiation therapy (RT) as a primary method of treatment was used in 72 patients (20.2%), chemotherapy (CT) in 76 (21.4%), and combined (RT + CT) therapy (CMT) in 208 cases (58.4%). The patients were followed from 6.3 to 26 years (median follow‐up was 13.7 years). For the whole group 5‐, 10‐, 15‐, 20‐, and 25‐year actuarial survival (S) rates were 90, 80, 74, 73, and 73%, respectively. The corresponding event‐free survival (EFS) rates were 63, 56, 56, 55, and 55%. The amelioration of the results was noted beginning with the 1973–1977 period, and for those treated in the last period (1983–1987) 5‐year S and EFS rates were 93 and 68%, respectively.

We conclude, that the modern treatment is also effective for our children suffering from HD. © 1995 Wiley‐Liss, Inc.
Prostatic non‐Hodgkin's lymphoma causing acute urinary retention in childhood
Authors: Li Chi‐Kong , Yeung Chung‐Kwong , Chow John , Shing Matthew , Chik Ki‐Wai , Liu Kelvin , Yuen Patrick
Published: February 2007

An 8‐year‐old boy presented with dysuria and acute retention of urine. Rectal examination showed a hard mass arising from the prostate. CT scan of the pelvis confirmed the presence of a large prostatic tumor causing bladder outflow obstruction. A provisional diagnosis of pelvic sarcoma was initially made. Biopsy of the tumor mass however, revealed non‐Hodgkin's lymphoma of T‐cell type. The tumor showed very good response to chemotherapy and the urinary obstruction significantly improved with a week after starting therapy. © 1995 Wiley‐Liss, Inc.
B‐cell non‐Hodgkin's lymphoma presenting as a primary renal tumour in a child
Authors: Vujanić Gordan M. , Webb David , Kelsey Anna
Published: February 2007

A 6‐year‐old boy presented with a unilateral renal tumour thought to be a Wilms' tumour. He had started a treatment but review of the histology and immunohistochemical studies proved the tumour to be a primary renal B‐cell lymphoma. This case illustrates the importance of an open‐minded approach in the histological examination of small round cell tumours in the kidney and immunohistochemical studies in such cases are strongly advocated. © 1995 Wiley‐Liss, Inc.
High‐dose‐rate brachytherapy in childhood sarcomas: A local control strategy preserving bone growth and function
Authors: Nag Subir , Olson Thomas , Ruymann Frederick , Teich Steven , Pieters Richard
Published: February 2007

The administration of external beam radiation therapy (EBRT) has been an integral part of the successful treatment of childhood sarcomas. However, EBRT has severe late morbidity in the developing child. In an attempt to deliver adequate tumoricidal radiation while preserving bone growth and organ function, 13 children with diverse sarcomas were treated with high dose rate brachytherapy (HDR). Seven patients had rhabdomyosarcoma and six patients had other soft tissue sarcoma variants. All patients were treated with disease‐appropriate chemotherapy, usually according to the Intergroup Rhabdomyosarcoma Study. Eleven patients received fractionated 36 Gy HDR alone at a mean of 3.5 months from diagnosis. Two patients received 10–12.5 Gy intraoperative HDR brachytherapy and additional 27 Gy EBRT. Nine of 11 patients in first remission have had no recurrences. One died of recurrent pulmonary metastases. The other patient that did recur is disease‐free 21 months post‐recurrence. Two additional patients were treated with HDR after tumor recurrence. One patient with recurrent Ewing's sarcoma, relapsed and died. The second is disease free 3 months after autologous bone marrow transplant. Grade 1 morbidity occurred in 46%, Grade 2 in 15%, and Grade 3 in 8% of the children, while relatively good bone and organ growth was maintained. The combination of conservative surgery, chemotherapy, and HDR offers the potential for disease control in young children while preserving bone growth and organ function. © 1995 Wiley‐Liss, Inc.
Simultaneous choriocarcinoma in mother and newborn infant
Authors: Picton Susan V. , Bose‐Haider Bratati , Lendon Mehroo , Hancock Barry W. , Campbell Richard H. A.
Published: February 2007

A male infant, born following an uncomplicated pregnancy, was severely anaemic at birth following significant foeto‐maternal haemorrhage. At three weeks of age a tumour was found in the liver with evidence of metastatic disease in the lungs. The infant died before treatment could be started. Postmortem revealed choriocarcinoma which led to subsequent diagnosis in the mother who also had pulmonary metastases. The mother has been successfully treated. The case is described in detail and followed by a discussion and a literature review of reported cases of simultaneous choriocarcinoma in infant and mother. © 1995 Wiley‐Liss, Inc.
A robust algorithm for configurational‐force‐driven brittle crack propagation with R‐adaptive mesh alignment
Authors: Miehe C. , Gürses E.
Published: February 2007

The paper considers a variational formulation of brittle fracture in elastic solids and proposes a numerical implementation by a finite element method. On the theoretical side, we outline a consistent thermodynamic framework for crack propagation in an elastic solid. It is shown that both the elastic equilibrium response as well as the local crack evolution follow in a natural format by exploitation of a global Clausius–Planck inequality in the sense of Coleman's method. Here, the canonical direction of the crack propagation associated with the classical Griffith criterion is the direction of the material configurational force which maximizes the local dissipation at the crack tip and minimizes the incremental energy release. On the numerical side, we exploit this variational structure in terms of crack‐driving configurational forces. First, a standard finite element discretization in space yields a discrete formulation of the global dissipation in terms configurational nodal forces. As a consequence, the constitutive setting of crack propagation in the space‐discretized finite element context is naturally related to discrete nodes of a typical finite element mesh. Next, consistent with the node‐based setting, the discretization of the evolving crack discontinuity is performed by the doubling of critical nodes and interface segments of the mesh. Critical for the success of this procedure is its embedding into an r‐adaptive crack‐segment reorientation procedure with configurational‐force‐based directional indicator. Here, successive crack releases appear in discrete steps associated with the given space discretization. These are performed by a staggered loading–release algorithm of energy minimization at frozen crack state followed by the successive crack releases at frozen deformation. This constitutes a sequence of positive‐definite discrete subproblems with successively decreasing overall stiffness, providing an extremely robust algorithmic setting in the postcritical range. We demonstrate the performance of the formulation by means of representative numerical simulations. Copyright © 2007 John Wiley & Sons, Ltd.
CEACAM1/VEGF cross‐talk during neuroblastic tumour differentiation
Authors: Poliani PL , Mitola S , Ravanini M , Ferrari‐Toninelli G , D'Ippolito C , Notarangelo LD , Bercich L , Wagener C , Memo M , Presta M , Facchetti F
Published: February 2007

The role of angiogenesis in tumour progression is a major subject in modern oncology and a correlation between angiogenesis and poor outcome has been demonstrated for human neuroblastomas. However, the role of angiogenesis in the maturation phase of neuroblastic tumours has never been considered. Human carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1), a potent pro‐angiogenic factor and mediator of vascular endothelial growth factor (VEGF)‐induced angiogenesis, plays a crucial role during the activation phase of angiogenesis and it has been shown to be expressed in the microvessels of the developing central nervous system as well as in newly formed immature blood vessels in many different tumours and under physiological conditions. The present study has investigated the role of CEACAM1/VEGF‐mediated angiogenesis across the whole spectrum of neuroblastic tumours, from undifferentiated to fully differentiated mature ganglioneuromas. CEACAM1 is peculiarly expressed in the microvessels of areas of active tumour maturation among differentiating neuroblastic/ganglion cells, whereas it is completely absent in the vessels of poorly differentiated/undifferentiated as well as in entirely mature Schwannian‐rich areas. Interestingly, VEGF expression has been found in differentiating neuroblastic/ganglion cells adjacent to CEACAM1‐positive microvessels. In keeping with these observations, VEGF expression was found in human neuroblastoma SH‐SY5Y cells during differentiation after retinoic acid treatment. Moreover, conditioned medium from SH‐SY5Y cells collected at different stages of differentiation induced progressive in vitro up‐regulation of CEACAM1 expression in human umbilical vein endothelial cells (HUVECs) that was abrogated by the specific VEGF receptor‐2/KDR inhibitor SU5416. Taken together, these data point to a role for CEACAM1/VEGF cross‐talk during the maturation phase of neuroblastic tumours. This may mimic physiological events leading to maturation of the vasculature in the developing normal central nervous system. On the other hand, in poorly differentiated/undifferentiated lesions, VEGF‐sustained angiogenesis does not reproduce physiological steps, but rather is associated with tumour aggressiveness and may involve other molecular pathways. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The changing shape of type 2 diabetes
Authors: Kerr D , Knott J , Cavan D
Published: February 2007

The aim of this study was to compare demographic and metabolic parameters of newly diagnosed patients presenting with type 2 diabetes over 10 years.

From postcode analyses we estimate that >90% of patients with new onset type 2 diabetes are referred to a structured nurse‐led education programme and are seen within one week of the diagnosis. Demographic and clinical data have been recorded since 1994.

Since 1994, there has been a 2.5‐fold increase in the number of patients diagnosed with type 2 diabetes in our area. At diagnosis, body mass index (BMI) has risen from 28.5 to 31.1kg/m2 (p<0.05) associated with a fall in HbA1c levels from 10.4% to 8.1% (p<0.0001) at presentation. There appears also to have been a gender difference with men presenting on average two years younger (mean difference 2.3 [95% CI 1.6–2.9] years, p<0.001) and with a lower BMI (‐1.6 [95% CI 1.3–2.0] kg/m2, p<0.001).

It was concluded that over the past 10 years there has been an increase in the number of patients presenting with new onset type 2 diabetes in our area. The lower HbA1c at diagnosis probably reflects earlier detection and awareness of the condition. There do appear to be gender differences with more men presenting earlier and with a lower BMI. Copyright © 2007 John Wiley & Sons.
Painless rupture of the Achilles tendon in a diabetic patient with sensory neuropathy
Authors: Gill GV , English PJ , Eyes B , Roland R , Pickin R
Published: February 2007

We describe a 71‐year‐old female diabetic patient with sensory distal lower limb neuropathy, who presented with painless swelling and erythema of the left ankle and lower shin. Diagnoses of cellulitis, deep venous thrombosis and Charcot neuroarthropathy were considered, but eventually a magnetic resonance scan showed complete rupture of the Achilles tendon. There was no history of trauma, and the absence of pain was presumed to be due to her dense sensory neuropathy. Copyright © 2007 John Wiley & Sons.
Crystal growth in alumina/poly(ethylene terephthalate) nanocomposite films
Authors: Yang Hoichang , Bhimaraj Praveen , Yang Lin , Siegel Richard W. , Schadler Linda S.
Published: February 2007

The crystal growth and morphology in 150‐nm‐thick PET nanocomposite thin films with alumina (Al2O3) nanoparticle fillers (38 nm size) were investigated for nanoparticle loadings from 0 to 5 wt %. Transmission electron microscopy of the films showed that at 1 wt % Al2O3, the nanoparticles were well dispersed in the film and the average size was close to the reported 38 nm. Above 2 wt % Al2O3, the nanoparticles started to agglomerate. The crystal growth and morphological evolution in the PET nanocomposite films kept at an isothermal temperature of 217 °C were monitored as a function of the holding time using in situ atomic force microscopy. It was found that the crystal nucleation and growth of PET was strongly dependent on the dispersed particles in the films. At 1 wt % Al2O3, the overall crystal growth rate of PET lamellae was slower than that of the PET homopolymer films. Above 2 wt % Al2O3, the crystal growth rate increased with nanoparticle loading because of heterogeneous nucleation. In addition, in these PET nanocomposite thin films, the Al2O3 nanoparticles induced preferentially oriented edge‐on lamellae with respect to the surface, which was not the case in unfilled PET as determined by grazing‐incidence X‐ray diffraction. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 747–757, 2007
A randomized trial of the effect of training in relaxation and guided imagery techniques in improving psychological and quality‐of‐life indices for gynecologic and breast brachytherapy patients
Authors: León‐Pizarro Concha , Gich Ignasi , Barthe Emma , Rovirosa Angeles , Farrús Blanca , Casas Francesc , Verger Eugènia , Biete Albert , Craven‐Bartle Jordi , Sierra Jordi , Arcusa Angeles
Published: February 2007

Purpose: The randomized study aimed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization.

Methods and materials: Sixty‐six patients programmed to receive brachytherapy in two hospitals in Barcelona (Spain) were included in this study. The patients were randomly allocated to either the study group (n=32) or the control group (n=34). Patients in both groups received training regarding brachytherapy, but only study group patients received training in relaxation and guided imagery. After collection of sociodemographic data, all patients were given a set of questionnaires on anxiety and depression: the Hospital Anxiety and Depression Scale (HADS), and on quality of life: Cuestionario de Calidad de Vida QL‐CA‐AFex (CCV), prior to, during and after brachytherapy.

Results: The study group demonstrated a statistically significant reduction in anxiety (p=0.008), depression (p=0.03) and body discomfort (p=0.04) compared with the control group.

Conclusions: The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety, depression and body discomfort in patients who must remain isolated while undergoing brachytherapy. This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy.

State: This study has passed Ethical Committee review. Copyright © 2007 John Wiley & Sons, Ltd.
Intraprostatic lymphatics in man: Light and ultrastructural observations
Authors: Furusato Masakuni , Mostofi F. K.
Published: February 2007

Despite reports that human prostate is without lymphatics, electron microscopic studies of prostatic curettings of human prostate have demonstrated unequivocal evidence that lymphatics exist in prostate proper. Such channels are found in two locations: between the muscle cells and in the fibrous stroma supporting the muscle bundles. The lymphatics between the muscle cells are of smaller caliber and probably represent initial lymphatics. They are intimately connected by anchoring filaments and microfibrils to the smooth muscle cells. The functional relationship between these has been discussed. No lymphatics were seen in subepithelial location. We saw only blood capillaries in that area.
The effect of therapy on the concentration and occupancy of androgen receptors in human prostatic cytosol
Authors: Mobbs B. G. , Johnson I. E. , Connolly J. G.
Published: February 2007

With a protamine sulphate precipitation method, total and free cytosol AR was assayed in BPH and prostatic carcinoma tissue, in order to investigate possible differences in AR concentration that might relate to the histopathology of the tissue or to endocrine manipulation of the patients. Similar ranges of total cytosol AR concentrations were observed in BPH and untreated prostatic carcinoma, but the latter tended to have a higher proportion of apparently free sites. Moreover, the proportion of “free” sites in the untreated carcinoma tissue appeared to be related to the proportion of poorly differentiated carcinoma in the specimen. In patients whose endogenous androgen levels had been lowered by treatment, the proportion of free sites tended to be higher, but a considerable proportion of sites appeared to be still occupied. Carcinoma tissue from some estrogen‐treated patients had high cytosol AR concentrations. It is suggested that, in some treated patients, androgens of adrenal origin may occupy some AR sites and that some carcinomas may contain a considerable concentration of nonfunctional AR.
Androgen and glucocorticoid receptors in the pollard prostate adenocarcinoma cell lines
Authors: Chan Sham Y.
Published: February 2007

Both the androgen and glucocorticoid receptors of the Pollard prostate adenocarcinoma cell lines (PA‐II and PA‐III) have been examined and characterized. Both cell lines contain distinct binding sites for 5α‐dihydrotestosterone (DHT) and dexamethasone (DM). The specific binding of the ligands to the whole cell was saturable, and Scatchard analysis showed a single class of high‐affinity and low‐capacity sites. (3H)‐DHT was bound to a cytosolic macromolecule which sedimented at 7S after sucrose density gradient centrifugation in low salt buffer, and was completely displaced by radioinert DHT. By means of competition studies, the androgen receptor could be distinguished from that for the glucocorticoids. The DNA and protein synthesis of both tumor lines were significantly enhanced after exposure to DHT.
Comparison of the R‐3327H rat prostatic adenocarcinoma to human benign prostatic hyperplasia and metastatic carcinoma of the prostate with regard to steroid hormone receptors
Authors: Dahlberg Erik , Snochowski Marek , Gustafsson Jan‐Åke
Published: February 2007

Quantitative analyses of cytosolic steroid hormone receptors were performed on nine tumors from the transplantable rat prostatic adenocarcinoma R‐3327H. Androgen receptors and estrogen receptors were found in eight of nine and five of six tumors, respectively. None of the tumors analyzed contained detectable progestin or glucocorticoid receptors (four and seven tumors, respectively). The apparent equilibrium dissociation constants for the androgen and estrogen receptors were 0.7‐4.3 nM and 0.6‐1.8 nM, respectively. The apparent equilibrium Bmax values (maximum number of binding sites) were 1,500‐25,000 fmoles/gm tissue for the androgen receptor and 640 to 5,800 fmoles/gm tissue for the estrogen receptor.

A comparison between the receptor contents of the R‐3327H rat tumor and human benign prostatic hyperplasia and metastatic carcinoma of the prostate showed that the rat tumor was different from the human tissues in several respects. Hence, the search for an optimal animal model for prostatic carcinoma in man must be continued.
Penicillanic acid derivatives in the canine prostate
Authors: Nielsen Ole S. , Frimodt‐Moeller Niels , Maigaard Svend , Hoyme Udo , Baumueller Axel , Madsen Paul O.
Published: February 2007

Distribution of ampicillin, amoxicillin, bacampicillin, mecillinam, pivmecillinam, carbenicillin, and carbenicillin indanyl sodium was studied in the canine prostate, prostatic interstitial fluid, and prostatic secretion. All seven antibiotics were found in higher concentrations in the prostatic interstitial fluid than in the prostatic secretion. As expected for weak acids, drug concentrations in these fluids were always lower than the simultaneous serum concentrations. Tissue penetration was enhanced for the penicillin ester, pivmecillinam, as shown by its prostatic secretion/ serum and tissue/serum ratios, which were higher than those of the other antibiotics, including the esters, bacampicillin, and carbenicillin indanyl sodium. This result may be due to pivmecillinam's long hydrolysis half‐life. The concentrations for these penicillanic acid derivatives in prostatic interstitial fluid were above the minimal inhibitory concentrations for most of the commonly encountered gram‐negative bacteria encountered in prostatitis. Therefore, these antibiotics should be effective in the treatment of bacterial prostatitis caused by susceptible organisms. Carbenicillin and carbenicillin indanyl sodium had the highest prostatic interstitial fluid/serum ratios of the compounds tested, and theoretically, therefore, they should be the most effective in the treatment of prostatitis. However, clinical trials should be carried out to confirm this.
Human prostatic adenocarcinoma: Some characteristics of a serially transplantable line in nude mice (PC 82)
Authors: Hoehn W. , Schroeder F. H. , Riemann J. F. , Joebsis A. C. , Hermanek P.
Published: February 2007

Transplantation of tissue from a cribriform human prostatic carcinoma resulted in a serially transplantable tumor line in nude mice, PC 82. During 2 1/2 years the tumor has not changed its histological appearance and remained a moderately differentiated adenocarcinoma. The cells contain large amounts of prostatic acid phosphatase. It has a slow rate of growth and regresses after castration and estrogen treatment. This preliminary information suggests that the PC 82 tumor line may be a suitable model for hormone‐dependent human prostatic cancer.
Thrombocytopenia during diethylstilbestrol diphosphate (stilphostrol) infusion for carcinoma of the prostate
Authors: Nachtsheim Daniel A. , McPherson Richard A. , Pollen Jeffrey J. , Schmidt Joseph D.
Published: February 2007

Transient thrombocytopenia was noted to occur in ten of 13 patients with advanced carcinoma of the prostate undergoing intravenous diethylstilbestrol diphosphate therapy. This was not associated with abnormalities of the initial platelet count or other parameters of the hemogram. There was no evidence of disseminated intravascular coagulation in these patients. No serious bleeding episodes occurred secondary to the thrombocytopenia. Following diethylstilbestrol diphosphate infusion, platelet counts generally returned to pretreatment levels. While the mechanism of action of the thrombocytopenia is unclear, we hypothesize a transient bone marrow toxicity as the cause of this phenomenon.
Zinc65 absorption in patients with carcinoma of the prostate
Authors: Spencer Herta , Kramer Lois , Osis Dace , Norris Clemontain , Evans Claudia
Published: February 2007

The intestinal absorption of 65Zn was determined in patients with carcinoma of the prostate prior to treatment and during estrogen therapy. Following an oral tracer dose of 65 ZnCl2, plasma levels and urinary and fecal excretions of 65Zn were determined. The absorption of 65Zn was low in six of eight patients, particularly in three patients who had extensive metastatic bone involvement. During estrogen therapy the absorption of 65Zn increased markedly in these patients, and this increase correlated with the clinical remission of the neo‐plastic process. In one patient who did not respond to estrogen therapy, 65Zn absorption was normal prior to treatment and did not increase during estrogen therapy. In patients free of neoplasia estrogen administration did not increase 65Zn absorption, and even decreased it. These results indicate that the intestinal absorption of 65Zn is decreased during the active phase of carcinoma of the prostate and improves during clinical remission induced by estrogen therapy.
The role of radiography, computed tomography and bone scanning in prostatic cancer
Authors: Pollen Jeffrey J.
Published: February 2007

This report reviews the roles of conventional radiography, computerized axial tomography, and nuclear bone scanning in the diagnosis, staging, follow‐up, and management of prostatic cancer. Computed tomography (CT) offers great promise for the better definition of the extent of the primary tumor of prostatic cancer. It contributes positively to the planning of radiation therapy portals in the treatment of localized disease. By means of bipedal lymphangiography and CT scanning, pelvic and periaortic lymphadenopathy may be detected more often than was previously possible without staging pelvic lymphadenectomy, which can be reserved for the discovery of microscopic disease. Soft‐tissue metastases that are located deep within the body cavities can now be measured accurately by CT scanning, as can their response to therapy. Skeletal metastases, the most common variety in prostatic cancer, can be detected with a high degree of sensitivity by nuclear bone imaging. Serial bone scans are remarkably useful in following the response of osseous deposits to treatment, as well as in detecting relapsing disease. The management of malignant obstruction of the ureters has been greatly facilitated by the application of angiographic techniques to percutaneous nephrostomy performed under fluoroscopic control.
Cryotherapy of prostate cancer
Authors: Loening Stefan , Hawtrey Charles , Bonney William , Narayana Ambati , Culp David A.
Published: February 2007

Cryosurgical destruction of primary adenocarcinoma of the prostate was performed via perineal route in 215 patients during a 12‐year period. The average age of the patients was 66 years. The stage of the disease varied from stage B to D. In 74% of the patients, no clinical evidence of tumor was found in the prostatic fossa following cryosurgery. Few patients needed transurethral surgery and none needed repeated transurethral resections for obstructive symptoms. This experience suggests that local destruction of prostatic carcinoma can be achieved with little morbidity and mortality. Herein we discuss the method of cryosurgery, stage and histology of tumor, survival, local recurrence, and complications.
Overview of past and current philosophy of prostatic cancer
Authors: Elder Jack S. , Scott William W. , Nyberg Leroy M.
Published: February 2007

Carcinoma of the prostate is the second most common cancer in men, yet no significant change in overall survival has occurred since the original description of the results of castration by Huggins and Hodges. Many important questions about the disease remain unanswered. The cause of prostatic cancer is unknown, and few specific environmental or viral agents have been linked with the tumor. Increased recognition of the importance of frequent digitial rectal examination has resulted in more tumors being diagnosed in early stages. Developments in sonography suggest that it may be useful in detecting the presence of prostatic cancer and whether extraprostatic extension has occurred. Recent improvements in the sensitivity of prostatic acid phosphatase assays have been made, but their use as a screening tool remains limited. In patients with clinical stage B lesions that are microscopically confined to the prostate, treatment by radical prostatectomy appears to confer greatest survival. The exact role of radiotherapy remains to be defined. However, when the tumor extends beyond the prostate and is localized to the pelvis, external beam or interstitial radiation is appropriate. Pelvic lymphadenectomy has significant morbidity, but less invasive methods of pelvic nodal evaluation are less accurate. Lymphadenectomy has not been shown to have any therapeutic effect. Whether hormonal therapy improves survival needs further investigation, and efforts must continue to develop means of predicting hormonal responsiveness. Those patients unlikely to respond to hormonal therapy should be treated with early chemotherapy.