bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metachronous Skeletal Osteosarcoma in Patients Treated with Adjuvant and Neoadjuvant Chemotherapy for Nonmetastatic Osteosarcoma
Authors: Aung LeLe , Gorlick Richard , Healey John H. , Shi Weiji , Thaler Howard T. , Shorter Nicholas A. , Huvos Andrew G. , Meyers Paul A. 
Published: January 2003

Purpose: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. Patients and Methods: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. Results: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. Conclusion: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.
Survivin, bcl-2, bax, and bcl-X Gene Expression in Sentinel Lymph Nodes From Melanoma Patients
Authors: Gradilone Angela , Gazzaniga Paola , Ribuffo Diego , Scarpa Susanna , Cigna Emanuele , Vasaturo Fortunata , Bottoni Ugo , Innocenzi Daniele , Calvieri Stefano , Scuderi Nicolo’ , Frati Luigi , Aglianò Anna Maria 
Published: January 2003

Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, bcl-X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma patients and then correlated to the outcome of patients. Patients and Methods: Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever possible, also by immunohistochemistry at the protein level. Results: We found a significant correlation (P < .005) between survivin expression and outcome of patients; in fact, 61.5% of patients expressing survivin gene progressed or died because of the disease, whereas 38.5% are currently disease-free. Among patients negative for survivin expression, 100% are disease-free after a median follow-up time of 52.9 months. We did not find a significant correlation between bcl-2, bax, and bcl-X gene expression and outcome of patients. In fact, these genes were found equally expressed in patients with disease progression and in disease-free patients. Conclusion: Our findings show a variable expression of apoptosis-related genes in SLNs of melanoma patients; more interestingly, we found that survivin expression correlates to outcome of patients in a statistically significant way, whereas the expression of other genes, such as bcl-2, bax, and bcl-X, did not seem to correlate to progression of disease. We suggest that the detection of survivin gene expression by RT-PCR in SLNs may be a useful prognostic indicator.
Humoral Immune Response to a Therapeutic Polyvalent Cancer Vaccine After Complete Resection of Thick Primary Melanoma and Sentinel Lymphadenectomy
Authors: Chung Mathew H. , Gupta Rishab K. , Hsueh Eddy , Essner Richard , Ye Wei , Yee Reynold , Morton Donald L. 
Published: January 2003

Purpose: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick (≥ 4 mm) primary cutaneous melanoma.Patients and Methods: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course.Results: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P = .184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P = .0006 and .006, respectively) but not with maximal IgG response (P = .73 and .95, respectively). Neither response predicted survival in the observation group.Conclusion: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.
The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the Afro‐Caribbean population of the Netherlands Antilles: A family screening
Authors: Westermann Cornelius J.J. , Rosina Ahlsen F. , de Vries Vanessa , Coteau Pamela A. de 
Published: January 2003

AbstractHereditary hemorrhagic telangiectasia (HHT) has been reported rarely in people of African descent. The prevalence in the Afro‐Caribbean population of the Netherlands Antilles is suspected to be high. A family screening in this population was done to arrive at a point prevalence and to identify patients with pulmonary involvement. By clinical history and physical examination, 219 persons over age twelve with a first‐degree relative with HHT were screened. The diagnosis was based on the new diagnostic criteria [Shovlin et al., 2000]. Chest‐roentgenogram and pulse‐oximetry or measurement of arterial oxygen pressure were used to detect pulmonary involvement. HHT was diagnosed in 112 individuals (51%), with at least a point prevalence of 1 in 1,331 inhabitants of Curaçao and Bonaire older than twelve years. The diagnosis was uncertain in 27; this was partly due to the new stringent criteria. Epistaxis was present in 98% and telangiectases in 99%. Facial telangiectases were relatively rare due to pigmented skin. Pulmonary involvement was found in 28% with serious—mainly neurological—complications in 48%. The point‐prevalence of HHT in the Afro‐Caribbean population of the Netherlands Antilles is the highest known in the world. Pulmonary involvement in this population is not rare and causes serious complications. © 2003 Wiley‐Liss, Inc.
Parental consanguinity and congenital heart malformations in a developing country
Authors: Nabulsi Mona M. , Tamim Hala , Sabbagh Maha , Obeid Mounir Y. , Yunis Khaled A. , Bitar Fadi F. 
Published: January 2003

AbstractThe association between isolated congenital heart defects and consanguinity was examined in 759 Lebanese patients with different types of congenital heart malformations. The subjects were patients of the Children's Cardiac Registry Center (CCRC) at the American University of Beirut Medical Center. The proportion of first‐cousin marriages among cardiac subjects was compared to that of the National Collaborative Perinatal Neonatal Network (NCPNN), after adjusting for the subjects' geographic distribution, and to the highest proportion reported by NCPNN. In general, the proportion of overall parental consanguinity and first‐cousin matings among CCRC subjects (34.7 and 20.2%, respectively) were significantly higher than the highest proportion of first‐cousin marriages reported by NCPNN (Bekaa subjects; 13.2%) (P < 0.0001). Comparison with the NCPNN‐adjusted first‐cousin mating proportion revealed a significantly increased rate of consanguinity in all categories of cardiac malformations except great vessel and coronary artery lesions (P < 0.05). The following lesions were significantly associated with increased parental consanguinity: aortic anomalies (aortic insufficiency, aortic stenosis, bicuspid aortic valve), atrial septal defect, double‐outlet right ventricle, pulmonary atresia, patent ductus arteriosus, pulmonic stenosis, tetralogy of Fallot, and ventricular septal defect (P < 0.05). Higher maternal education was the only variable that was negatively correlated with parental consanguinity (P = 0.037). Our study emphasizes the role of homozygous recessive genes in the causation of different types of isolated congenital heart malformations, known to follow a multifactorial pattern of inheritance. There is an urgent need for educating the public on the deleterious effects of inbreeding, especially in developing countries with high overall consanguinity rates and limited financial resources. © 2003 Wiley‐Liss, Inc.
Patient with Sotos syndrome, Wolff‐Parkinson‐White pattern on electrocardiogram, and two right‐sided accessory bypass tracts
Authors: Sharma Param P. , Vidaillet Humberto , Dietz Julie 
Published: January 2003

AbstractSotos syndrome is a growth regulation disorder. Accessory conduction pathways, the anatomical structures responsible for Wolff‐Parkinson‐White syndrome, are thought to result from developmental failure to eradicate the remnants of the atrioventricular connections during cardiogenesis. Although the reported prevalence of congenital heart disease in Sotos syndrome is 10 times higher than in the general population, there are no reported cases with ventricular pre‐excitation. We report a patient with Sotos syndrome with two distinct accessory atrioventricular bypass tracts documented by invasive electrophysiology testing and a curative catheter ablation procedure. © 2003 Wiley‐Liss, Inc.
Unknown diagnosis in two male cousins with facial abnormalities, optic atrophy, abnormal EEG, and severe psychomotor retardation
Authors: Mégarbané André 
Published: January 2003

AbstractWe report two male cousins with short stature, microcephaly, hypertelorism, optic atrophy, ptosis, absent ear lobes, high‐arched palates, abnormal EEG, and severe mental retardation. Both cousins have consanguineous parents. Differential diagnoses are discussed and the possibility that we might be reporting on a new syndrome is raised. © 2003 Wiley‐Liss, Inc.
Patient with terminal duplication 3q and terminal deletion 5q: comparison with the 3q duplication syndrome and distal 5q deletion syndrome
Authors: Angle Brad , Yen Frank , Hersh Joseph H. , Gowans Gordon 
Published: January 2003

AbstractPartial duplication of chromosome 3q is a well‐described condition of multiple congenital anomalies and developmental delay that resembles the Brachmann‐de Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome has recently been described. The combination of both chromosome abnormalities has not been previously described. We report on a child with both a de novo duplication of distal 3q (q27 → qter) and terminal deletion of 5q (q35.2 → qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate developmental delays. The phenotype is compared and contrasted to the few reports of patients with similar terminal 3q duplications and 5q deletions. Our patient did not have the characteristic phenotype of the 3q duplication syndrome, suggesting that the chromosome region responsible for this phenotype is more proximal than the terminal 3q27 region. In addition, comparison with three other reported cases of terminal 5q35 deletions suggests a possible association of terminal 5q deletions with central nervous system (CNS) structural abnormalities. © 2003 Wiley‐Liss, Inc.
Gaucher disease associated with parkinsonism: Four further case reports
Authors: Várkonyi Judit , Rosenbaum Hanna , Baumann Nicole , MacKenzie Jennifer J. , Simon Zsuzsa , Aharon‐Peretz Judith , Walker Jamie M. , Tayebi Nahid , Sidransky Ellen 
Published: January 2003

AbstractType 1 Gaucher disease is considered the non‐neuronopathic form of this autosomal recessively inherited lysosomal storage disease. We report the simultaneous occurrence of Gaucher disease with parkinsonian in four adult patients. The patients had a relatively early onset of parkinsonian manifestations, and their disease was rapidly progressive and refractory to therapy. Each had a different Gaucher genotype, although four alleles carried the common N370S mutation. No mutations were identified in the genes for parkin or α‐synuclein. The concurrence of these two phenotypes, both in this series of patients and in others in the literature, suggests a shared pathway, modifier, or other genetic etiology. Published 2003 Wiley‐Liss, Inc.
Speech characteristics in the Kabuki syndrome
Authors: Upton Sheila , Stadter Carmella S. , Landis Pat , Wulfsberg Eric A. 
Published: January 2003

AbstractSix children with Kabuki syndrome were studied to investigate speech patterns associated with the syndrome. Each child's speech was characterized with regard to articulation (types of errors and intelligibility), pitch (high or low), loudness (volume of speech), and prosody (general quality of speech that combines rate and inflection). All six children had a history of delayed speech and language acquisition and were receiving speech services. All individuals had articulation errors and abnormal oral resonance, which appeared to be due to poor oral‐motor coordination and hypotonia and were not felt to be due to structural abnormalities such as velopharyngeal insufficiency, dental malocclusion, or cleft palate. An intriguing finding, noted in the two individuals followed from childhood into adolescence with serial speech evaluations, was that pitch, loudness, and prosody did not mature over time and what was age appropriate performance at younger ages became inappropriate in adolescence. This raises a challenge for speech services, as by adolescence, while articulation had improved, the pitch and loudness of these individuals' speech had not and so was noticeably different from peers. Distinctive speech characteristics with a lack of normal maturation during childhood can be added to the extensive list of clinical features associated with the Kabuki syndrome and hopefully will lead to improved speech/language treatment for individuals with this syndrome. © 2003 Wiley‐Liss, Inc.
Parents' and children's attitudes toward the enrollment of minors in genetic susceptibility research: Implications for informed consent
Authors: Bernhardt Barbara A. , Tambor Ellen S. , Fraser Gertrude , Wissow Lawrence S. , Geller Gail 
Published: January 2003

AbstractPurpose: Children at high risk of future disease may be recruited for participation in disease susceptibility research involving genetic testing. This study was aimed at assessing parents' and children's reactions to such research, and their perceptions of risks and benefits of participating. Methods: Parents and children (ages 10–17) from families at increased risk for breast cancer (n = 16 dyads) and heart disease (n = 21 dyads) participated in separate audiotaped interviews and a follow‐up family interview one year later. We asked about reactions, risks and benefits, and informational needs regarding participation in hypothetical research involving genetic testing on a saliva sample. Audiotape transcripts were analyzed qualitatively. Results: All children would initially participate because they viewed the research as low risk. When thinking about learning their test result and sharing it with others, or the uncertainties of testing, many children became hesitant about participating. Many parents thought their child might worry about a positive result, making them unlikely to enroll their child, or to choose not to tell the child test results. Both children and parents thought the benefits of participating included early detection or treatment (breast cancer families), prevention (heart disease families) and helping others. Children's questions about research participation centered on details of the study design and purpose, while parents' questions related to the genetic test itself. Conclusions: Children's first reaction to participating in research involving genetic susceptibility testing research may not indicate an adequate appreciation of risks and benefits; if encouraged to personalize the impact of genetic testing, children are able to engage in a more informed decision‐making process. © 2003 Wiley‐Liss, Inc.
An angel with Down syndrome in a sixteenth century Flemish Nativity painting
Authors: Levitas Andrew S. , Reid Cheryl S. 
Published: January 2003

AbstractArtistic representation of malformation syndromes has been of ongoing interest, often as a point of departure for discussion of medical history. We have identified a 16th‐century Flemish Nativity painting in which one angelic figure appears distinctly different from other individuals in the painting with an appearance of Down syndrome. Several prior observers have identified Down syndrome in premodern art, sometimes stimulating ongoing discussions concerning its history, its prevalence, and its relationship to hypothyroidism. This may be one of the earliest European representations of Down syndrome. The depiction of an individual with Down syndrome as an angel raises several questions regarding the status of such an individual in late medieval times and societal recognition of minor anomalies, as contrasted with major malformations, in their predictive value for disabilities. In contrast, Langdon Down's description of the condition occurred only after evolution of concepts regarding the clinical significance of physical appearance and measurement. © 2003 Wiley‐Liss, Inc.
Double supernumerary isodicentric chromosomes derived from 15 resulting in partial hexasomy
Authors: Qumsiyeh Mazin B. , Rafi Syed K. , Sarri Catherine , Grigoriadou Maria , Gyftodimou Jolanda , Pandelia Effie , Laskari Hara , Petersen Michael B. 
Published: January 2003

AbstractWe report two unrelated patients each with two supernumerary marker chromosomes (SMCs) derived from chromosome 15, and thus resulting in partial hexasomy. Hexasomy in the one case (family 1) was diagnosed at prenatal diagnosis and did not include the Prader–Willi/Angelman critical region (PWACR). The double SMCs were also found in the mother, the pregnancy continued to term, and an apparently phenotypically normal child was born. This represents the first report of transmission of double SMCs from mother to child. In the second case (family 2), the hexasomy did include the PWACR and was de novo in origin. This patient manifested severe psychomotor retardation, clefting of the soft palate, hypotonia, seizure‐like episodes, and other phenotypic features. The aberrant phenotype is attributable to the hexasomy for the PWACR gene loci. The normal homologs of chromosome 15 proved to be biparental in origin while the two SMCs appeared maternal. © 2003 Wiley‐Liss, Inc.
Clinical variability of type II sialidosis by C808T mutation
Authors: Rodríguez Criado G. , Pshezhetsky A.V. , Rodríguez Becerra A. , Gómez de Terreros I. 
Published: January 2003

AbstractSialidosis (McKusick 256550) is an autosomal recessive disorder resulting from mutations in the NEU gene, located in 6p21.3, which leads to deficiency of alpha‐N‐acetyl neuraminidase (sialidase) activity, causing an accumulation of its substrates, oligosaccharides, in the lysosomes of various organs and tissues and an increased presence in urine and other organic fluids. We present a clinical report of three patients diagnosed for type II sialidosis. The first patient is a 12‐year‐old boy with the classic infantile form. His sister had a congenital form of sialidosis and died at 20 months of age. The third, nonrelated patient presented shortly after 1 year of age and had borderline cognitive delay at 9 years. All three patients were homozygous for the C808T mutation of the NEU gene. Their ancestors originated from a small area to the east of the city of Seville (Spain), suggesting the existence of a Seville founder mutation. © 2002 Wiley‐Liss, Inc.
Apparent encephalocele in twin fetus papyraceus with twin‐reversal arterial perfusion
Authors: Gilbert‐Barness Enid , Opitz John M. , Chamyan Gabriel , Debich‐Spicer Diane 
Published: January 2003

AbstractAn apparently iniencephalic or exencephalic monoamniotic monochorionic female twin fetus, delivered as a fetus papyraceus at 28 weeks of gestation, had severe anomalies of the central nervous system and spine, including occipital encephalocele with a defect of the occipital bone. The encephalocele contained a spherical mass of autolyzed brain tissue without identifiable cerebellum or vermis. The cervical canal was widely patent dorsally, there were severe bony anomalies, including agenesis and fusion of vertebrae in the cervicothoracic spine. The upper limbs were absent. All organs were hypoplastic and autolyzed. The hypoplastic heart had three chambers. The placenta was monochorionic and monoamniotic; barium injection showed a twin‐reversal arterial perfusion and entanglement of the umbilical cords. © 2002 Wiley‐Liss, Inc.
Griscelli syndrome without hemophagocytosis in an eleven‐year‐old girl: Expanding the phenotypic spectrum of Rab27A mutations in humans
Authors: Aksu Güzide , Kütükçüler Necil , Genel Ferah , Vergin Canan , Omowaire Benjamin 
Published: January 2003

AbstractWe present an eleven‐year‐old female patient who was referred to us with silvery hair, hepatosplenomegaly, neutropenia‐thrombocytopenia, hypogammaglobulinemia and degenerative white matter disease, with a family history of a female sibling dying at the age of five and two living male cousins, ages 10 and 11. She had been followed up for her cytopenia the last three years and had totally recovered from a hemiplegic episode before admission. The family was of Arabic origin, and a second‐degree consanguinity was reported between the parents. Microscopic analysis of her hair shafts revealed irregularly distributed small and large clumps of melanin, and skin biopsy findings were consistent with partial albinism. Bone marrow aspiration and biopsy did not detect any evidence of hemophagocytosis. Genetic analysis identified a homozygous two‐base‐pair deletion (51 del CT leading to S18X) in the Rab27A gene of the patient. She suffered from febrile neutropenic episodes. Her persistent cytopenia could not be corrected with immunoglobulin, thrombocyte infusions, or a short course of growth factor treatment. Splenectomy was planned due to her progressive splenic enlargement. She was also considered for bone marrow transplantation. She unfortunately died from an intracranial hemorrhage. Her clinical presentation was remarkable, mostly resembling partial albinism immunodeficiency/Elejalde syndrome due to her older age and absence of hemophagocytosis, but with molecular findings confirming Griscelli syndrome. © 2002 Wiley‐Liss, Inc.