bluuebunny/crossref_metadata_2025 huggingface dataset:
Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma
Authors: Castiglia Daniele , Pagani Elena , Alvino Ester , Vernole Patrizia , Marra Giancarlo , Cannavò Elda , Jiricny Josef , Zambruno Giovanna , D'Atri Stefania
Published: April 2003

Inactivation of mismatch repair (MMR) genes has been linked to the hereditary nonpolyposis colon cancer syndrome and to a subset of sporadic cancers. A phenotypic characteristic of tumors with defective MMR is microsatellite instability (MSI). Although MSI has been reported in a proportion of cutaneous melanomas, inactivation of MMR genes in this tumor type has not been detected thus far. We recently described a human melanoma cell line, PR‐Mel, and a cutaneous metastasis from the same patient, which displayed a MMR defect, and showed high MSI. Here we report that in the PR‐Mel cell line both MLH1 alleles are somatically inactivated. One allele is lost through a chromosomal deletion of the region 3p21–24, whereas the remaining allele harbors a G → A transition at position −1 of the acceptor splice site of intron 15, leading to the in‐frame skipping of exon 16. The primary melanoma of the PR patient shows loss of heterozygosity at the BAT21 microsatellite marker, located in the MLH1 gene, and does not express the MLH1 and PMS2 proteins. Moreover, it harbors the same mutation detected in the PR‐Mel cells. These results demonstrate that biallelic inactivation of MLH1 had occurred in the primary melanoma of the PR patient and suggest that disruption of MMR might have had a role in the development of the melanoma. This is the first report in which genetic defects leading to disruption of MMR function in a human melanoma have been identified. © 2003 Wiley‐Liss, Inc.
Analysis of genetic stability at the EP300 and CREBBP loci in a panel of cancer cell lines
Authors: Tillinghast Guy W. , Partee Jason , Albert Paul , Kelley Jenny M. , Burtow Kenneth H. , Kelly Kathleen
Published: April 2003

EP300 (p300) and CREBBP (CBP) are highly related transcriptional co‐activators possessing histone acetyltransferase activity. These proteins have been implicated in coordinating numerous transcriptional responses that are important in the processes of proliferation and differentiation. A role for EP300 and CREBBP as tumor suppressors in cancer has been suggested by the fact that they are targeted by viral oncogenes; there is an increased incidence of hematologic malignancies in mice monoallelic for CREBBP; and loss, albeit at a low frequency, of both EP300 alleles in epithelial cancers has been observed. Because the level of EP300/CREBBP appears to have a critical effect on integrating certain transcriptional processes, we sought to determine whether a loss in the combined gene dosage of EP300 and CREBBP might play a role in cancer. Accordingly, we screened a panel of 103 cell lines for loss of heterozygosity and found 35 and 51% LOH for the CREBBP and EP300 loci, respectively. Concordant loss of CREBBP and EP300 was not associated with mutations in important regions of the remaining EP300 or CREBBP genes. In addition, there did not appear to be a statistically significant selection in cancer cells, stratified by various criteria, for the concordant loss of EP300 and CREBBP. We conclude that EP300 and CREBBP rarely act as classical tumor suppressors in human cancer. Published 2003 Wiley‐Liss, Inc.
Genome‐wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation‐mediated fusion events
Authors: Debernardi Silvana , Lillington Debra M. , Chaplin Tracy , Tomlinson Simon , Amess John , Rohatiner Ama , Lister T. Andrew , Young Bryan D.
Published: April 2003

Gene expression profiles were determined from presentation peripheral blood and bone marrow samples of 28 patients with acute myeloid leukemia (AML). Hierarchical clustering sorted the profiles into separate groups, each representing one of the major cytogenetic classes in AML [i.e., t(8;21), t(15;17), inv(16), 11q23, and normal karyotype]. Statistical group comparison identified genes whose expression was strongly correlated with these chromosomal classes. Moreover, the normal karyotype AMLs were characterized by distinctive up‐regulation of certain members of the class I homeobox A and B gene families, implying a common underlying genetic lesion. These data reveal novel diagnostic and therapeutic targets and demonstrate the potential of microarray‐based dissection of AML. © 2003 Wiley‐Liss, Inc.
Near‐diploid and near‐triploid human sporadic colorectal adenocarcinomas differ for KRAS2 and TP53 mutational status
Authors: Giaretti Walter , Venesio Tiziana , Sciutto Andrea , Prevosto Claudia , Geido Elio , Risio Mauro
Published: April 2003

Mutations of the KRAS2 protoncogene and inactivation of the TP53 oncosuppressor gene have been suggested to contribute to chromosomal instability (CIN) and aneuploidy in colorectal cancer (CRC). Previous work has also shown that the degree of DNA ploidy [DNA index (DI)], as obtained by flow cytometry in CRC, is non‐randomly distributed and, in particular, that DI near‐diploid and near‐triploid values are well separated by a low‐probability valley region. At present, it is not known whether a relationship exists between DI and the mutational status of KRAS2 and TP53. Multiple samples obtained from 35 human sporadic CRCs have been used to provide nuclei suspensions for flow cytometric analysis and sorting of specific DI subpopulations. Sorted nuclei were then used to analyze the high‐microsatellite‐instability (MSI‐H) phenotype and the mutation spectrum of the KRAS2 and TP53 genes. A single MSI‐H case was detected. There were 6 DNA diploid (DI = 1) and 29 aneuploid (DI ≠ 1) CRCs, with the DI aneuploid cases non‐randomly subdivided in 9 near‐diploid (DI ≠ 1 and DI ≤ 1.4), 8 near‐triploid (1.4 < DI < 1.6), and 12 high‐aneuploid (DI ≥ 1.6) cases. Proximal CRCs were more often DNA diploid and near‐diploid than distal ones, and Dukes' C cases were more commonly high‐aneuploid than Dukes' B. Moreover, the incidence of mutations of the KRAS2 and TP53 genes was lowest among the DNA near‐triploid subpopulations and highest among the near‐diploid ones. We suggest that DNA near‐diploid and near‐triploid subpopulations in human sporadic CRC reflect different genetic mechanisms of CIN and have a potentially different clinical behavior. © 2003 Wiley‐Liss, Inc.
Identification of CBL, a proto‐oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia
Authors: Fu Jen‐Fen , Hsu Jia‐Jong , Tang Tzung‐Chih , Shih Lee‐Yung
Published: April 2003

We have shown that the CBL gene at 11q23.3, telomeric to MLL, was fused to MLL in an adult patient with de novo acute myeloid leukemia (FAB‐M1). Southern blot analysis indicated that the MLL rearrangement was involved in the chromosomal abnormality. cDNA panhandle polymerase chain reaction identified the fusion transcript, in which MLL exon 6 was fused in‐frame with CBL exon 8. Long‐distance PCR amplified the genomic junction region, which involved the fusion of the 3′ portion of an Alu element in intron 6 of MLL with the 5′ portion of an Alu element in intron 7 of CBL. The absence of extensive sequence similarity at both breakpoints of MLL and CBL indicated that the recombination was not generated through homologous recombination. MLL and CBL are located between STS markers D11S939 and D11S924. Analysis of the sequence demonstrated that the transcriptional orientation of both genes at 11q23.3 is from centromere to telomere. The results of Southern blotting in conjunction with fluorescence in situ hybridization suggest that the MLL‐CBL fusion was the result of an interstitial deletion. CBL, a proto‐oncogene, functions as a negative regulator of several receptor protein–tyrosine‐kinase signaling pathways and as an adaptor protein in tyrosine phosphorylation‐dependent signaling. CBL is the second gene at 11q23.3 found to fuse with MLL. © 2003 Wiley‐Liss, Inc.
Increased expression of the LGALS3 (Galectin 3) gene in human non–small‐cell lung cancer
Authors: Yoshimura Akinobu , Gemma Akihiko , Hosoya Yoko , Komaki Eriko , Hosomi Yukio , Okano Tetsuya , Takenaka Kiyosi , Matuda Kuniko , Seike Masahiro , Uematsu Kazutsugu , Hibino Suguru , Shibuya Masahiko , Yamada Tesshi , Hirohashi Setsuo , Kudoh Shoji
Published: April 2003

Patients with lung cancer have a poor prognosis because of the high metastatic potential of the neoplasm. Therefore, identifying new molecular targets for anti‐metastatic therapy is very important. To identify novel key factors of tumor metastasis in lung cancer, we established the gene expression profiles of two adenocarcinoma cell line variants, PC9/f9 and PC9/f14, by use of genome‐wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line, PC9. The PC9/f9 and PC9/f14 cell lines were selected for analysis because of their high metastatic potential. We identified five genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression and that had not been reported to be involved in metastasis of lung cancer. One of the overexpressed genes that was identified encoded the β‐galactoside–binding protein LGALS3 (Galectin 3). LGALS3 has been reported to be overexpressed in a variety of human cancers, but not in lung cancer, and to be involved in tumor metastasis. We examined the expression of LGALS3 by use of real‐time quantitative reverse transcription–polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy. A population (10/30) of the non–small‐cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells. In contrast, all small‐cell lung cancers either failed to express the gene or expressed it at a very low level. The mean of the relative expression of the LGALS3 gene in non–small‐cell lung cancer (3.065 ± 3.976) was significantly higher than those of small‐cell lung cancer (0.02 ± 0.03) (P < 0.025). This is the first report of alterations of LGALS3 gene expression in lung cancer. These results, together with the previous reports on Galectin 3 function, suggest that Galectin 3 may play a role in the process of metastasis in non–small‐cell lung cancer that overexpresses Galectin 3, but not in small‐cell cancer. Accordingly, LGALS3 may be a phenotypic marker that excludes small‐cell lung cancer and may represent a novel target molecule in non–small‐cell lung cancer therapy. © 2003 Wiley‐Liss, Inc.
Complete physical map and gene content of the human NF1 tumor suppressor region in human and mouse
Authors: Jenne Dieter E. , Tinschert Sigrid , Dorschner Michael O. , Hameister Horst , Stephens Karen , Kehrer‐Sawatzki Hildegard
Published: April 2003

Duplicon‐mediated microdeletions around the NF1 gene are frequently associated with a severe form of neurofibromatosis type I in a subgroup of patients who show an earlier onset of cutaneous neurofibromas, dysmorphic facial features, and lower IQ values. To clarify the discrepancies between published maps of the NF1 tumor‐suppressor gene region as well as the length of gaps in these assemblies and to validate the recently described tandem duplication of the human NF1 locus, we assembled a contiguous high‐density map of BAC and PAC clones from different genomic libraries. Although two WI‐12393–derived low‐copy fragments are known to occur at the proximal and distal boundaries of the 1.5‐Mb segment that is usually deleted in NF1 microdeletion patients, we identified an additional WI‐12393–related segment between the MGC13061 and the NF1 gene, which appears to trigger interstitial deletions of smaller size as observed in two patients. Moreover, we completed the genomic organization and cDNA structure of all functional genes, CYTOR4, FLJ12735, FLJ22729, CENTA2, MGC13061, NF1, OMG, EVI2B, EVI2A, KIAA1821, MGC11316, HCA66, KIAA0160, and WI‐12393, from this region. A comparison of the human map to the orthologous region on mouse chromosome 11 revealed significant differences in the number and arrangement of genes, indicating that many chromosomal breaks with partial duplications, inversions, and deletions occurred predominantly in the primate lineage. © 2003 Wiley‐Liss, Inc.
A novel fusion gene, SS18L1/SSX1, in synovial sarcoma
Authors: Storlazzi Clelia Tiziana , Mertens Fredrik , Mandahl Nils , Gisselsson David , Isaksson Margareth , Gustafson Pelle , Domanski Henryk A. , Panagopoulos Ioannis
Published: April 2003

Synovial sarcoma is an aggressive soft tissue tumor that is characterized cytogenetically by the t(X;18)(p11;q11) translocation, resulting in fusion between the SS18 gene on chromosome 18 and one of the SSX genes on the X chromosome. The three fusion genes that have been detected thus far, SS18/SSX1, SS18/SSX2, and SS18/SSX4, account for more than 95% of the synovial sarcomas. Because SS18/SSX fusions do not seem to occur in other tumor types, and because synovial sarcomas may sometimes be difficult to distinguish from other spindle cell tumors, molecular genetic analysis has become established as an important diagnostic tool. Upon cytogenetic analysis of a soft‐tissue tumor that showed classic synovial sarcoma morphology, we detected two supernumerary marker chromosomes but no rearrangement of chromosomes X or 18. By fluorescence in situ hybridization, the marker chromosomes were shown to contain material from chromosomes X and 20, including the SSX gene cluster on the X chromosome and the SS18L1 gene, which shows strong homology with the SS18 gene, on chromosome 20. Further RT‐PCR analysis and sequencing of the amplified products revealed a novel SS18L1/SSX1 fusion transcript in which nucleotide 1216 (exon 10) of SS18L1 was fused in‐frame with nucleotide 422 (exon 6) of SSX1. Thus, the existence of genetic heterogeneity has to be taken into account when RT‐PCR is used for the diagnosis of synovial sarcoma. © 2003 Wiley‐Liss, Inc.
Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers
Authors: Tan Duan‐Jun , Chang Julia , Chen Woan‐Ling , Agress Lesley J. , Yeh Kun‐Tu , Wang Baotyan , Wong Lee‐Jun C.
Published: April 2003

Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis because of its high susceptibility to oxidative DNA damage and limited repair mechanisms. For investigation of the potential role of somatic mtDNA mutations in the tumorigenesis of oral cancer, we screened the occurrence of mtDNA mutations by the temporal temperature gradient gel electrophoresis method. We amplified the entire mitochondrial genome by use of 32 pairs of overlapping primers, and to identify the mutations, we sequenced DNA fragments showing different banding patterns between normal and tumor mtDNA. Fourteen of eighteen (77.8%) oral carcinomas displayed somatic mtDNA mutations, with a total of 26 mutations. Among them, six were in the mRNA coding region. Three were missense mutations (C14F, H186R, T173P) in NADH dehydrogenase subunit 2, and one was a frameshift mutation, 9485delC, in cytochrome c oxidase subunit III. Eight (44%) tumors had insertion or deletion mutations in the nucleotide position 303–309 poly C region of the D‐loop. Multiple large deletions were also observed. Our results demonstrate that somatic mtDNA mutations occur in oral cancer. Some missense and frameshift mutations may play an important role in the tumorigenesis of this carcinoma. More extensive biochemical and molecular studies will be necessary for determining the pathologic effect of these somatic mutations. © 2003 Wiley‐Liss, Inc.
Radiation therapy for recurrent orbital hemangioma
Authors: Mierzwa Michelle L. , Barrett William L. , Gluckman Jack L.
Published: April 2003

Background.

Surgical resection and corticosteroid therapy have traditionally been the preferred methods of treatment for orbital hemangioma. Radiation therapy is not usually indicated because of the potential for ocular complications. With modern radiation techniques, however, patients may experience substantial clinical improvement without significant radiation‐induced morbidity.

Methods.

A case of unresectable, recurrent orbital hemangioma is described. The clinical presentation, management protocol using radiation therapy, and 5‐year follow‐up are reviewed.

Results.

The patient was initially seen with left orbital pain, diplopia, proptosis, and conjunctival edema caused by a recurrent left orbital hemangioma after failed previous surgery. CT scan and angiogram revealed a large, irregular, multilocular mass in the left orbit consistent with hemangioma. The patient was treated with a total of 2000 cGy in 10 treatments. Five‐year follow‐up revealed a stable, regressed hemangioma with no radiation complications.

Conclusions.

Radiation therapy may be used if appropriately indicated for function‐threatening orbital hemangioma. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Complications in transoral CO2 laser surgery for carcinoma of the larynx and hypopharynx
Authors: Vilaseca‐González Isabel , Bernal‐Sprekelsen Manuel , Blanch‐Alejandro José‐Luis , Moragas‐Lluis Miguel
Published: April 2003

Background.

Because of the increase in indications for laser surgery to treat malignant tumors of the larynx and hypopharynx, a higher number of complications may be expected. We prospectively evaluated the frequency and characteristics of intraoperative and postoperative complications of early and advanced tumors of the larynx and hypopharynx treated with CO2 laser surgery and the potential influence of the surgical learning curve on the complication rate.

Methods.

Two hundred seventy‐five patients operated in a tertiary referral center. Complications were classified either as major, requiring intensive medical treatment, blood transfusion, surgery, or ICU admission, or minor, resolving spontaneously or with conventional ambulatory treatment without sequelae. The surgical learning curve was analyzed by dividing the patients into two groups according to the date of surgery and then comparing the number of complications.

Results.

Complications occurred in 18.9% of patients; 9.8% were considered major and 9.1% minor. Complications included local infection (0.7%), emphysema (1%), cutaneous fistula (0.3%), postoperative bleeding (8%), airway ignition (0.3%), dyspnea (because of edema or stenosis) (1.8%), and swallowing difficulties or aspiration pneumonia (6.1%). The complication rate correlated significantly with tumor extension (p < .0001), the presence of diabetes mellitus (p = .01), and less surgical experience (p < .0001). Complications with severe sequelae occurred in two patients (p = .7).

Conclusions.

Complications after transoral laser surgery of larynx and hypopharynx carcinomas are relatively frequent (18.9%), but serious sequelae and mortality rate are low. Complications are associated with tumor extension, limited surgical experience, and diabetes mellitus. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Diagnostic delays in laryngeal carcinoma: Professional diagnostic delay is a strong independent predictor of survival
Authors: Teppo Heikki , Koivunen Petri , Hyrynkangas Kalevi , Alho Olli‐Pekka
Published: April 2003

Background.

Clinical stage at the time of diagnosis is the most important determinant of prognosis in cancers of the head and neck. Accordingly, delay in diagnosis could worsen survival in laryngeal cancer, although this hypothesis has not been verified in previous studies.

Methods.

To determine the effects of patient and professional diagnostic delays on survival in patients with laryngeal squamous cell carcinoma (LSCC), a population‐based sample of 66 patients with LSCC in Northern Finland between 1990 and 1995 was investigated. In addition to clinical data from tertiary care units and mortality data from the national death register, we collected data about the first medical visit in primary care that resulted, subsequently, in the diagnosis of malignancy.

Results.

Long professional delay in diagnosis (≥12 months) was an independent and statistically significant determinant of worsened prognosis (adjusted relative hazard of death 4.74, p = .05). There was no correlation between patient delay and prognosis. Another significant factor related to impaired prognosis was advanced stage (IV vs I–III, adjusted relative hazard of death 5.18, p = .02). Long professional delay was not significantly related to any of the demographic or clinical characteristics.

Conclusions.

A long professional delay is a marked and independent determinant of impaired survival in laryngeal carcinoma and equals the effect of advanced stage. However, unlike in most other cancers, early symptoms and slow tumor growth give the physician a fairly long time to reach the correct diagnosis before the delay turns out to be fatal. © 2003 Wiley Periodicals, Inc. Head Neck 25:000–000, 2003
Significance of the juxtaoral organ (of Chievitz)
Authors: Pantanowitz Liron , Balogh Karoly
Published: April 2003

Background.

Most physicians are unaware of the juxtaoral organ (of Chievitz) and its clinical significance. The aim of this review is to draw attention to the clinical importance of this organ.

Methods.

Review and interpretation of the English and non‐English literature pertaining to the juxtaoral organ.

Results.

The juxtaoral organ is a small structure located within the soft tissue overlying the angle of the mandible in the buccotemporal space. It is composed of an epithelial parenchyma embedded in a highly organized connective tissue stroma rich in nerves and sensory receptors innervated by the buccal nerve. This metabolically active structure presumably serves as a mechanosensor in the lateral wall of the oral cavity. Needless surgical removal of this juxtaoral structure is therefore best avoided. In children, the normal organ may be discovered as a small mass in the cheeks, which may lead to extensive and unnecessary investigations. Hyperplasia of the parenchyma may occur, but carcinoma originating from this organ has not been reported.

Conclusion.

Awareness of this normal anatomic structure is important, because the finding of epithelial islands intimately admixed with nerves could be misinterpreted as perineural invasion by carcinoma. © 2002 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Myeloma of the jaw bones: A clinicopathologic study of 33 cases
Authors: Lae Marick E. , Vencio Eneida F. , Inwards Carrie Y. , Unni K. Krishnan , Nascimento Antonio G.
Published: April 2003

Background.

A clinicopathologic study of 33 cases of plasma cell neoplasm of the jaw bones was performed.

Methods.

The Mayo Clinic's pathology files through 1995 were reviewed for cases of plasma cell neoplasia involving the jaw bones. Clinical data, radiologic features, and follow‐up data were obtained from the hospitals of origin, referring physicians, and Mayo Clinic files. The histopathologic features of the 33 tumors were studied.

Results.

There were 21 (64%) male and 12 (36%) female patients, ranging in age from 25 to 81 years (mean, 57.7 years). Twenty‐one tumors (64%) were classified as solitary plasmacytoma of bone (SPB) and 12 (36%) as multiple myeloma (MM). Among the SPB cases, 15 (71%) involved the maxilla, and 14 patients were men, with a mean age of 57.1 years. Abnormal serum protein was found in 22% of patients, and in nine patients (43%) the SPB converted to MM after a median of 20.7 months. Among the MM cases, seven (58%) affected the maxilla, seven patients were men with mean age of 58.3 years, and abnormal serum protein and Bence‐Jones protein were found in 42% and 73% of the patients, respectively. Anaplastic histology was identified in seven (33%) SPB and six (50%) MM tumors, and amyloid was present in eight (38%) SPB and three (25%) MM tumors. Twelve (57%) SPB patients died of the disease after a median disease‐free survival of 6.75 years, and the overall and disease‐free survival rates at 5 and 10 years were 52%, 33%, 33%, and 24%, respectively. All MM patients died of the disease after a median survival of 17.6 months, and the 5‐year and 10‐year survival rates were 8% and zero. Eighty‐six percent of the SPB patients with anaplastic histologic findings died of the disease (average survival, 3.8 years), whereas only 43% of those with classic histologic findings died of the disease (average survival, 11.75 years). Among MM patients, anaplastic histologic findings were associated with a 9‐month average survival (26‐month average survival for MM patients with classic histologic findings).

Conclusions.

SPB patients seem to have a better prognosis than MM patients, and 43% of SPB tumors convert to MM after an average of 20.7 months. Anaplastic histologic findings seem to be associated with lower survival rates and periods for SPB patients and lower survival periods for MM patients. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Intraoperative neck staging using sentinel node biopsy and imprint cytology in oral cancer
Authors: Asthana Sonal , Deo S.V. Suryanarayana , Shukla Nootan K. , Jain Paresh , Anand Mona , Kumar Rajive
Published: April 2003

Background.

Nodal status is an important prognostic factor in oral cancer. Sentinel node studies may enable accurate identification of high‐risk nodes without a formal neck dissection. Imprint cytology is an emerging tool to assist in the rapid intraoperative detection of nodal metastases with encouraging results in other solid tumors. This study was planned to evaluate a novel method of intraoperative staging using sentinel node biopsy and intraoperative imprint cytology in oral cancer.

Patients and Methods.

Thirty‐two cases of oral cancer underwent sentinel node mapping using 1% isosulfan blue during the study period. The sentinel node was sent for evaluation by imprint cytology. The average time taken for reporting was 15 minutes. The result was compared with the final histopathology, which was taken as the “gold standard”.

Results.

Sentinel nodes (SLN) were identified in 30 cases (93.75% identification rate), with two false negatives. Intraoperative imprint cytology (IIC) could accurately predict the nodal status in 28 of the 30 patients. There was one false‐positive result and one false‐negative result. The overall sensitivity, specificity, and accuracy of IIC were 87.5%, 95.4%, and 93.3 %, respectively.

Conclusion.

Sentinel node biopsy along with IIC provides a reliable, inexpensive, and accurate method of intraoperative identification of the nodal status in oral cancer. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Health profiles and quality of life of 518 survivors of thyroid cancer
Authors: Schultz Pamela N. , Stava Charles , Vassilopoulou‐Sellin Rena
Published: April 2003

Background.

Available literature describes the long‐term outcome of thyroid cancer survivors with respect to thyroid cancer but not their overall medical and social well‐being.

Methods.

Five hundred eighteen thyroid cancer survivors responded to a survey regarding medical and social impacts of their cancer experience.

Results.

All had surgery, and 417 (80.5%) also had some radiation. Two thirds (64.5%) reported that cancer created health effects varying by gender and passage of time; neurologic, musculoskeletal, and psychologic problems seemed most prominent. They reported more memory loss and psychologic problems than other cancer survivors and more migraine headaches than both other cancer survivors and the general population. Regarding family and work, they integrated well in society overall. However, unsolicited comments by 24.5% of responders disclosed symptoms reminiscent of thyroid hormone imbalance.

Conclusion.

Thyroid cancer survivors generally report good health long term but describe distinct, lasting medical problems including symptoms of thyroid dysregulation. The extent and manner in which cancer therapy contributes to the health profile of the group merits further inquiry. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Ruptured internal jugular vein: A postoperative complication of modified/selected neck dissection
Authors: Cleland‐Zamudio Suzanne S. , Wax Mark K. , Smith James D. , Cohen James I.
Published: April 2003

Background.

Postoperative hemorrhage from the internal jugular vein after a modified or selective neck dissection is an infrequent, yet potentially life‐threatening, complication. Despite the increasing frequency of modified or selective neck dissections, this complication has not been previously highlighted in the literature.

Setting.

Tertiary referral academic center.

Material and Methods.

The records of six patients who experienced this complication were reviewed and analyzed for risk factors that might predict its occurrence.

Results.

Common risk factors included postoperative pharyngeal fistula formation, significant tobacco history, and poor nutritional status. A more complete circumferential dissection of the vein low in the neck in the presence of hypopharyngeal fistula may place it at a higher risk for rupture.

Conclusions.

Patients who have a complete circumferential dissection of the internal jugular vein low in the neck and go on to have fistulas develop may be more prone to internal jugular vein rupture. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Argyrophilic nuclear organizer regions in nasopharyngeal carcinoma and paraneoplastic epithelia
Authors: Chen Maohuai , Lee Joseph C. K. , Lo Shikyuen , Shen Jian
Published: April 2003

Background.

Nucleolar organizer regions (NORs), which are loops of DNA containing ribosomal RNA genes, have been shown to correlate with cell proliferation and malignant transformation. The diagnostic value of silver staining NORs (AgNORs) in preneoplastic epithelia and nasopharyngeal carcinoma (NPC) by the quantitative assessment of AgNORs proteins is evaluated.

Methods.

Silver‐staining of NORs was applied to 70 paraffin sections of NPC biopsy specimens, including 29 samples of the adjacent normal glandular epithelia (GE), 19 hyperplastic/dysplastic columnar epithelia (CE) in the adjacent mucosa, 10 hyperplastic/dysplastic squamous epithelia (SE) in the adjacent mucosa, 54 differentiated nonkeratinizing carcinoma (DC), and 16 undifferentiated carcinoma (UC). The morphometric features of AgNORs in preneoplastic epithelia and cancer cells were analyzed by image cytometric analysis and then compared.

Results.

The AgNOR count, mean AgNOR area, and AgNOR area–count ratio increased significantly from GE to CE to DC or UC. The mean nuclear area, AgNOR area, and AgNOR area–count ratio increased significantly from GE to SE to UC, whereas overlapping AgNOR values were observed between SE and DC. UC had significantly higher values than DC in mean nuclear area, AgNOR area, and AgNOR area–count ratio.

Conclusions.

The morphometric analysis of AgNORs reflected cell proliferative activity and histologic differentiation of tumor rather than malignant transformation in different nasopharyngeal epithelia and NPC. AgNOR area and AgNOR area–count ratio are the most valuable features for differential diagnosis of normal, preneoplastic, and cancer cells. © 2003 Wiley Periodicals, Inc. Head Neck 25:000–000, 2003
Severe trismus secondary to periosteal osteogenesis after fibula free flap maxillary reconstruction
Authors: Smith Russell B. , Funk Gerry F.
Published: April 2003

Background.

Fibula free tissue transfer is routinely used for reconstruction of bony defects in the head and neck. During flap preparation, well‐vascularized periosteum is left adjacent to the proximal vascular pedicle. It is known that periosteum can have significant osteogenic potential in the proper settings. Complications related to periosteal osteogenesis of a fibula free flap pedicle have not been previously reported.

Case History.

A 12‐year‐old girl with a history of squamous cell carcinoma of the maxilla underwent delayed fibula free flap reconstruction of a maxillary defect. The patient had severe trismus develop postoperatively and was found to have osteogenesis along the vascular pedicle. This bone formed a solid bridge from the maxilla to the mandible. Two resections were required, which included excision of the vascular pedicle, to eliminate further osteogenesis and resolve the patient's trismus.

Conclusions.

The potential for periosteal osteogenesis does exist with fibula free tissue transfer and can have significant consequences. Potential promoters of osteogenesis should be identified and if possible altered in certain clinical scenarios to prevent complications from new bone growth. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
A study of the effect of a resistive heat moisture exchanger (trachinaze) on pulmonary function and blood gas tensions in patients who have undergone a laryngectomy: A randomized control trial of 50 patients studied over a 6‐month period
Authors: Jones Andrew Simpson , Young Pamela Elizabeth , Hanafi Zul Bin , Makura Zorustra George Grange , Fenton John Elian , Hughes Joseph Peter
Published: April 2003

Background.

Previous work from this department has shown that resistive tracheostomy filters increase the partial pressure of oxygen in capillary blood and also provide a significant amount of heat/moisture exchange. Until now it has not been shown whether there is any long‐term beneficial effect and in particular whether raised tissue oxygenation is maintained using a practical filter device.

Methods.

We carried out a 6‐month randomized control trial including 50 laryngectomees. Twenty‐five patients were treated with the Liverpool Heat Moisture Exchange device incorporating an airway resistor (Trachinaze). Another 25 patients were treated with a placebo device. Relevant subjective and objective data were collected before and at the end of the study. The objective measurements were capillary oxygen tension (which parallels blood arterial tension), carbon dioxide tension, FEV1, FVC, and PIF. Patients were reviewed at intervals throughout the study. Data were analyzed using the Mann–Whitney U test and the paired t test to test the difference between the active device and placebo at 6 months.

Results.

Subjective lower airway parameters, including cough, number of chest infections, mucus production, and shortness of breath at rest, were significantly improved in the active group compared with the placebo group. The objective parameters FEV1, FVC, and PIF were not significantly different. Capillary oxygen tension, however, was highly significantly raised in the active group at 6 months.

Conclusions.

Trachinaze is highly superior to placebo at improving subjective pulmonary parameters, including shortness of breath. It is also superior in its ability to maintain an increased peripheral tissue oxygen tension over a 6‐month period. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Learning associations between places and visual cues without learning to navigate: Neither fornix nor entorhinal cortex is required
Authors: Gaffan E.A. , Bannerman D.M. , Healey A.N.
Published: April 2003

Rats with fornix transection, or with cytotoxic retrohippocampal lesions that removed entorhinal cortex plus ventral subiculum, performed a task that permits incidental learning about either allocentric (Allo) or egocentric (Ego) spatial cues without the need to navigate by them. Rats learned eight visual discriminations among computer‐displayed scenes in a Y‐maze, using the constant‐negative paradigm. Every discrimination problem included two familiar scenes (constants) and many less familiar scenes (variables). On each trial, the rats chose between a constant and a variable scene, with the choice of the variable rewarded. In six problems, the two constant scenes had correlated spatial properties, either Allo (each constant appeared always in the same maze arm) or Ego (each constant always appeared in a fixed direction from the start arm) or both (Allo + Ego). In two No‐Cue (NC) problems, the two constants appeared in randomly determined arms and directions. Intact rats learn problems with an added Allo or Ego cue faster than NC problems; this facilitation provides indirect evidence that they learn the associations between scenes and spatial cues, even though that is not required for problem solution. Fornix and retrohippocampal‐lesioned groups learned NC problems at a similar rate to sham‐operated controls and showed as much facilitation of learning by added spatial cues as did the controls; therefore, both lesion groups must have encoded the spatial cues and have incidentally learned their associations with particular constant scenes. Similar facilitation was seen in subgroups that had short or long prior experience with the apparatus and task. Therefore, neither major hippocampal input–output system is crucial for learning about allocentric or egocentric cues in this paradigm, which does not require rats to control their choices or navigation directly by spatial cues. Hippocampus 2003;13:445–460. © 2003 Wiley‐Liss, Inc.
Comparison of computational models of familiarity discrimination in the perirhinal cortex
Authors: Bogacz Rafal , Brown Malcolm W.
Published: April 2003

This study compares the efficiency and plausibility of published computational models of familiarity discrimination in the perirhinal cortex. Substantial evidence indicates that the perirhinal cortex is involved in both the familiarity discrimination aspect of recognition memory and in perceptual functions involved with representations of complete stimuli (i.e., object identification). Published models of how the perirhinal cortex may perform familiarity discrimination can be divided into two groups. The first group assumes that a proportion of perirhinal neurons form a network specialised just for familiarity discrimination (these models may be based on Hebbian or anti‐Hebbian synaptic plasticity). In contrast, the second group assumes that both familiarity discrimination and learning representations of complete stimuli are performed within a single combined network. This study establishes that when the responses of neurons that provide input to the familiarity discrimination network are correlated (as indicated by experimental data), specialised networks based on anti‐Hebbian learning may recognise the previous occurrence of many more stimuli (i.e., have a capacity up to thousands of times larger) than specialised networks based on Hebbian learning. The currently published combined models do not learn an optimal stimulus representation (they do not fully extract statistically independent features), and hence their capacities are even lower than those of the specialised models based on Hebbian learning. Hence, the combined models published thus far are critically less efficient than the specialised models based on anti‐Hebbian learning. This study also compares the consistency of the models with experimental observations concerning what is known of synaptic plasticity in the perirhinal cortex and the responses of its neurons. Many theoretically important parameters remain undetermined, and experiments are suggested to provide information critical for refining and distinguishing between the various models. However, the above theoretical arguments and currently published data favour the existence of a separate network specialised for familiarity discrimination. Hippocampus 2003;13:494–524. © 2003 Wiley‐Liss, Inc.
Different actions of Gabapentin and baclofen in hippocampus from weaver mice
Authors: Bertrand Sandrine , Morin France , Lacaille Jean‐Claude
Published: April 2003

The pre‐ and postsynaptic effects of baclofen, a broad‐spectrum γ‐aminobutyric acid (GABA)B receptor agonist, and gabapentin, a selective agonist at GABAB receptors composed of GABAB(1a,2) heterodimers, were examined in CA1 pyramidal cells using whole‐cell patch‐clamp recordings in hippocampal slices from different strains of mice. In slices from C57BL/6 mice, by means of GABAB receptors, gabapentin and baclofen activated outward K+ currents at resting membrane potential. In weaver mice with a Kir3.2 channel mutation, baclofen and gabapentin failed to activate postsynaptic K+ currents. However, in littermate controls of weaver mice, gabapentin failed to evoke K+ currents, whereas baclofen activated currents in the same cells. Thus, postsynaptic actions of gabapentin and baclofen on K+ currents are different in this mouse strain. Via presynaptic GABAB receptors, baclofen significantly reduced GABAA inhibitory postsynaptic currents (IPSCs) in slices from C57BL/6 mice, as well as weaver and control mice. In contrast, gabapentin did not affect IPSCs significantly in any group of mice. These results indicate that although baclofen and gabapentin are agonists at postsynaptic GABAB receptors positively coupled to K+ channels, their mechanism of action differs in certain strains of mice, including the weaver wild‐type mice, suggesting a dissociation in their signaling mechanism and coupling to K+ channels. Hippocampus 2003;13:525–528. © 2003 Wiley‐Liss, Inc.
Bacterial meningitis causes two distinct forms of cellular damage in the hippocampal dentate gyrus in infant rats
Authors: Bifrare Yoeng‐Delphine , Gianinazzi Christian , Imboden Hans , Leib Stephen L. , Täuber Martin G.
Published: April 2003

Bacterial meningitis causes neurological sequelae in up to 50% of survivors. Two pathogens known for their propensity to cause severe neurological damage are Streptococcus pneumoniae and group B streptococci. Some forms of neuronal sequelae, such as learning and memory deficits, have been associated with neuronal injury in the hippocampus. To learn more about hippocampal injury in meningitis, we performed a comparative study in bacterial meningitis due to S. pneumoniae and group B streptococcus, in which 11‐day‐old infant rats were infected intracisternally with either of the two pathogens. Histopathological examination of the neuronal injury in the dentate gyrus of the hippocampus showed that S. pneumoniae caused predominantly classical apoptotic cell death. Cells undergoing apoptosis were located only in the subgranular zone and stained positive for activated caspase‐3 and TUNEL. Furthermore, dividing progenitor cells seemed particularly sensitive to this form of cell death. Group B streptococcus was mainly responsible for a caspase‐3‐independent (and TUNEL‐negative) form of cell death. Compared with the morphological features found in apoptosis (e.g., apoptotic bodies), this form of neuronal death was characterized by clusters of uniformly shrunken cells. It affected the dentate gyrus throughout the blade, showing no preferences for immature or mature neurons. Thus, depending on the infecting agent, bacterial meningitis causes two distinct forms of cell injury in the dentate gyrus. Hippocampus 2003;13:481–488. © 2003 Wiley‐Liss, Inc.
Reactions to familiar and novel objects in infant monkeys with neonatal temporal lesions
Authors: Meunier Martine , Nalwa Vanit , Bachevalier Jocelyne
Published: April 2003

Adult monkeys with late temporal lobe damage are known to touch and mouth objects compulsively, even unknown objects. To determine whether infants with early temporal damage display this symptom as well, 9‐month‐old rhesus monkeys with neonatal ablations of either the medial temporal lobe or inferior temporal cortex were exposed to four objects, two familiar and two novel. All operated infants were less active/more withdrawn than controls and showed neither exaggerated object manipulation nor hyperorality. Furthermore, like controls, they touched novel objects less than they touched familiar ones. Thus, infants with neonatal medial or inferior temporal ablations did not display the compulsive exploration evidenced after similar lesions in adulthood and retained some ability to detect novelty despite their known memory impairments. Hippocampus 2003;13:489–493. © 2003 Wiley‐Liss, Inc.
Measuring method of three thermophysical parameters of solids by a thermal probe with instantaneous point contact: Measuring principle
Authors: Takahashi Ichiro , Emori Masaaki
Published: April 2003

A new method for instantaneous measurement of three thermophysical parameters of solids in situ is proposed. The measurement principle is based on a transient heat conduction model of a thermal probe point contacting a testing body. The measurement of temperature response has been made using the probe of a sheathed K‐type thermocouple in this experiment. Ratios of both thermal conductivity and thermal effusivity between the probe and the testing body are determined from curve‐fitting with the theoretical response to the measured one. As a result, it is shown that the measurement is reproducible and the accuracies of measured thermophysical parameters are good enough to apply this method to many kinds of solids. © 2003 Wiley Periodicals, Inc. Heat Trans Asian Res, 32(3): 191–201, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10084
Measuring method of three thermophysical parameters of solids by a thermal probe with instantaneous point contact: Discussion about applicability and measuring conditions
Authors: Takahashi Ichiro , Emori Masaaki
Published: April 2003

An instrument for the measuring method reported in the previous paper is a handy tester for three thermophysical parameters of solids in situ. Discussions about measurement errors caused by not strictly satisfying the measuring conditions, such as size and shape of the testing body, and about optimum initial temperature difference between thermal probe and testing body have been done. As a result of the experiment varying the shape of a probe end, it is shown that the radius of the contacting surface on a testing body has no influence on measuring thermophysical parameters. © 2003 Wiley Periodicals, Inc. Heat Trans Asian Res, 32(3): 202–211, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10085
Solution to shape identification problem of unsteady heat‐conduction fields
Authors: Katamine Eiji , Azegami Hideyuki , Matsuura Yasuhiro
Published: April 2003

This paper presents a numerical analysis method for shape determination problems of unsteady heat‐conduction fields in which time histories of temperature distributions on prescribed subboundaries or time histories of gradient distributions of temperature in prescribed subdomains have prescribed distributions. The square error integrals between the actual distributions and the prescribed distributions on the prescribed subboundaries or in the prescribed subdomains during the specified period of time are used as objective functionals. Reshaping is accomplished by the traction method that was proposed as a solution to shape optimization problems of domains in which boundary value problems are defined. The shape gradient functions of these shape determination problems are derived theoretically using the Lagrange multiplier method and the formulation of material derivative. The time histories of temperature distributions are evaluated using the finite‐element method for a space integral and the Crank–Nicolson method for a time integral. Numerical analyses of nozzle and coolant flow passage in a wing are demonstrated to confirm the validity of this method. © 2003 Wiley Periodicals, Inc. Heat Trans Asian Res, 32(3): 212–226, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10086