bluuebunny/crossref_metadata_2025 huggingface dataset:
Obturator canal fat plug: A pre‐hernial condition?
Authors: Callaghan C.J. , Whitaker R.H.
Published: October 2002

Although obturator hernias are rare, they are associated with a high mortality, as diagnosis is often delayed and the condition tends to occur in the elderly. Previous researchers have postulated that obturator hernias begin with invagination of pre‐peritoneal fat through the pelvic orifice of the obturator canal, forming a fat plug. With chronically raised intra‐abdominal pressure, or sudden weight loss, this can progress to a clinical obturator hernia. We dissected 95 Caucasian cadaveric hemi‐pelvises (47 males; 48 females) in order to investigate the frequency of fat plugs and examine the validity of the current hypothesis regarding obturator hernia pathogenesis. The mean age (SD) of the specimens was 83 (9) years, with 48 (24 male; 24 female) from the left side and 47 (23 male; 24 female) from the right side. A fat plug was found in 21 canals (22%); the majority were female (71%, P = 0.03), and right sided (62%, P = 0.20). The mean (SD) length was 20.0 mm (6.3 mm), with mean diameter 5.9 mm (1.8 mm). A shallow peritoneal dimple was also found overlying fat plugs in two specimens. No visceral herniations were found. The sex and side distribution of the obturator canal fat plugs we found are similar to those of obturator hernias reported in the literature, supporting the hypothesis that fat plugs are pre‐hernial. It is unlikely that fat plugs are a high‐risk condition, but dimples over these plugs may be a marker of potential hernia formation. Clin. Anat. 15:276–279, 2002. © 2002 Wiley‐Liss, Inc.
Computer programs for estimating substrate flux into steady‐state biofilms from pseudoanalytical solutions
Authors: Goudar Chetan T. , Strevett Keith A.
Published: October 2002

Fixed‐film processes employing microorganisms attached to an inert surface (biofilms) are widely used for biological treatment of municipal and industrial wastewater. For optimal design and analysis of these processes, mathematical models are necessary that describe the dynamics of contaminant transport within these biofilms and the associated contaminant utilization by the microorganisms. However, these governing equations that typically involve Fickian diffusion for contaminant transport and Monod kinetics for contaminant utilization are inherently nonlinear and have no closed form solutions except under special conditions. This can restrict their use in the classroom as cumbersome numerical techniques must be used for their solution. This problem is well documented in the literature and several authors have presented pseudoanalytical solutions that replace numerical solutions with algebraic equations. In the present study, we present pseudoanalytical solution‐based computer programs for estimating substrate flux and biofilm thickness for a steady‐state biofilm. Depending upon the intended end use, these programs can either partially or totally automate the solution process. In the partial automation mode, they can serve to enhance student understanding of important concepts related to steady‐state biofilms, while complete automation can help bring more challenging and realistic problems associated with steady‐state biofilms into the classroom. The programs have been tested on MATLAB version 5.0 and are available as freeware for educational purposes. © 2002 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 26–32, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10017
Maintaining a focus on the child? First impressions of the Framework for the Assessment of Children in Need and their Families in cases of child neglect
Authors: Horwath Jan
Published: October 2002

The Framework for the Assessment of Children in Need and their Families is guidance introduced by the Department of Health in England to improve assessment practice and promote better outcomes for children and their families. This paper considers ways in which the Assessment Framework can improve assessment practice in cases of child neglect. However, as with any national guidance, its effectiveness is dependent on local approaches to implementation. The author has undertaken practice development work around implementation with senior managers and frontline staff in area child protection committees (ACPCs) and social services departments. These experiences are used to explore the local issues and tensions encountered by both practitioners and managers responsible for implementing the Assessment Framework. An argument is made that these issues and tensions if not addressed can result in distorted assessments that lose the focus on the child. Copyright © 2002 John Wiley & Sons, Ltd.
A novel use of the Amplatzer muscular ventricular septal defect occluder
Authors: Thanopoulos Basil (Vasilios) D. , Georgakopoulos Dimitrios J. , Tsaousis George S. , Eleftherakis Nicholas G.
Published: October 2002

We report a case of a 12‐month‐old‐infant with double outlet right ventricle and pulmonary stenosis who presented with signs of superior vena cava syndrome secondary to a dysfunctioning bidirectional Glenn shunt. The patient was successfully treated with transcatheter obstruction of an accessory pulmonary blood flow using the Amplatzer muscular ventricular septal defect occluder. Cathet Cardiovasc Intervent 2002;56:234–237. © 2002 Wiley‐Liss, Inc.
Comparison of outcomes after 8 vs. 9.5 French size intra‐aortic balloon counterpulsation catheters based on 9,332 patients in the prospective Benchmark® registry
Authors: Cohen Marc , Ferguson James J. , Freedman Robert J. , Miller Michael F. , Reddy Ramachandra C. , Ohman E. Magnus , Stone Gregg W. , Christenson Jan , Joseph Debra L.
Published: October 2002

The Benchmark intra‐aortic balloon counterpulsation (IABC) registry maintains prospectively gathered clinical information on a large cohort of IABC patients. The purpose of the present report is to compare in‐hospital outcomes and complications in patients treated with the newer 8 vs. 9.5 Fr size catheters. Between January 1997 and August 2000, data on 7,078 9.5 Fr and 2,254 8 Fr IABC insertions were submitted to Benchmark. This was not a randomized comparison but rather a posthoc analysis of prospectively gathered data. There was less limb ischemia with the 8 Fr IABC size catheter. There were no significant differences in bleeding or mortality between the two groups. Smaller IABC catheter size is associated with significantly less limb ischemia, especially in higher‐risk patients. The large, population‐based, ongoing Benchmark registry provides a useful vehicle for outcomes research concerning the evolving practice of IABC. Cathet Cardiovasc Intervent 2002;56:200–206. © 2002 Wiley‐Liss, Inc.
Coronary perforation as a potential complication derived from coronary thrombectomy with the X‐Sizer device
Authors: Sanmartín Marcelo , Goicolea Javier , Ruiz‐Salmerón Rafael , Mantilla Ramón , Sterling Juán , Meneses Daniel , Calvo Francisco
Published: October 2002

We report a case of coronary perforation after failed atherectomy with a 2 mm X‐Sizer catheter in recent totally occluded right coronary artery. The perforation was successfully managed with a polytetrafluoroethylene‐covered stent with satisfactory final angiographic results. Possible predictors of this complication with this new device are discussed. Cathet Cardiovasc Intervent 2002;56:378–382. © 2002 Wiley‐Liss, Inc.
Percutaneous interventions in patients with cocaine‐associated myocardial infarction: A case series and review
Authors: Sharma Arvind K. , Hamwi Shadi M. , Garg Nidhi , Castagna Marco T. , Suddath William , Ellahham Samer , Lindsay Joseph
Published: October 2002

Cocaine‐associated myocardial infarction (CAMI) is a well‐reported entity. Most previous reports on CAMI have been limited to conservative care utilizing benzodiazepines, aspirin, nitroglycerin, calcium channel blockers, and thrombolytics. Current guidelines on CAMI advocate immediate use of angiography and angioplasty if available rather than routine administration of thrombolytics. However, based on literature search from 1966 to 2001 (using keywords “cocaine,” “myocardial infarction,” and “angioplasty”), there have been only two case reports of percutaneous coronary intervention (PCI) in patients with cocaine‐associated myocardial infarction. Both were notable for complications either during or immediately after the procedure. We report a series of 10 patients with cocaine‐associated myocardial infarction who were treated with percutaneous interventions, which included angioplasty, stenting, and AngioJet mechanical extraction of thrombus. Despite the different arteriopathic process involved, our findings suggest that PCI can be performed safely and with a high degree of procedural success in patients with CAMI. Cathet Cardiovasc Intervent 2002;56:346–352. © 2002 Wiley‐Liss, Inc.
Less invasive PTCA of a gastroepiploic artery combining the transradial approach and 5 Fr guiding catheter: A case report
Authors: Sharma Gyarsi Lal , Louvard Yves , Tavolaro Oscar , Lefèvre Thierry , Loubeyre Christophe , Dumas Pierre , Morice Marie‐Claude
Published: October 2002

The gastroepiploic artery has been successfully used as an arterial conduit in selected patients undergoing CABG with acceptable immediate and long‐term results. Myocardial ischemia may occur during the follow‐up period as a result of spasm, occlusion, or stenosis at the anastomosis site. Because of tortuosity and in order to avoid graft spasm and to obtain good extra backup support, we require low‐profile wide‐lumen guiding catheters for deep intubation and increased procedural success. In the case presented here, a gastroepiploic graft stenosis was treated by balloon angioplasty performed through a less invasive approach combining transradial access and use of 5 Fr guiding catheter. Cathet Cardiovasc Intervent 2002;56:494–497. © 2002 Wiley‐Liss, Inc.
Thrombosis of a patent foramen ovale closure device: Thrombolytic management
Authors: Vanderheyden Marc , Willaert Willem , Claessens Philip , Branders Inge , Ex Paul , Vermeersch Paul
Published: October 2002

Transcatheter closure of a patent foramen ovale (PFO) offers a valuable alternative to surgery in selected patients with presumed paradoxical embolism. Like for all other devices, several complications have been described. Although the majority of these complications are caused by technical problems of the device itself, thrombosis is a relatively infrequent but feared finding, as it may result in recurrent embolic events and persistent neurological deficits. The majority of the complications after implantation are dealt with by surgical removal of the device and subsequent surgical closure of the PFO. The present case report describes biatrial thrombosis of a PFO device that was successfully treated with thrombolytics and GP IIb/IIIa receptor blockers. In stable patients, this pharmaco‐therapeutic approach should be attempted to save the thrombosed PFO device and could therefore offer a valuable alternative to surgical removal of the device. Cathet Cardiovasc Intervent 2002;56:522–526. © 2002 Wiley‐Liss, Inc.
An equivalence relation between parallel calibration and principal component regression
Authors: Fugate Michael L. , Christensen Ronald , Hush Don , Scovel Clint
Published: October 2002

Multivariate calibration and prediction, when there are few observations and many variables, is an important and unresolved problem in chemometrics. Recently a technique called paralle calibration was introduced as a new and easy to understand calibation method. In this paper we show that parallel calibration is equivalent to a form of principal component regression and to generalized inverse regression. Copyright © 2002 John Wiley & Sons, Ltd.
A theoretical study of the transmutation method for resolving and quantifying overlapped chromatographic bands
Authors: Malinowski Edmund R.
Published: October 2002

Recently, a new chemometric technique called ‘transmutation’ has been designed to convert overlapping chromatographic bands into narrow bands, sufficient for resolving and quantifying the components. The ‘transmutation function’ is generated from the chromatogram of the component of interest, recorded with the same instrument and experimental conditions used to record the unresolved chromatogram of the sample mixture. The original method was based on the assumption that the shapes of the overlapping chromatographic bands are proportionately congruent (i.e. exact same shapes but different intensities). This condition was fulfilled in the early study because the band overlap region was confined to a narrow time window. The present study represents a theoretical investigation of the effects of band broadening and extends the method to include chromatograms that violate the congruency requirement. The method is applicable to single‐detector as well as multiple‐detector systems. Copyright © 2002 John Wiley & Sons, Ltd.
Resolution of LC/1H NMR data applied to a three‐component mixture of polyaromatic hydrocarbons
Authors: Shen Hailin , Airiau Christian Y. , Brereton Richard G.
Published: October 2002

A three‐component mixture of naphthalene, anthracene and pyrene with the middle peak embedded was recorded using LC/1H NMR. Two case‐studies, one with tailing peaks and one without, were analysed. A procedure was developed involving apodization, Fourier transformation, phasing and baseline correction of raw data, preprocessing by frequency shift and peak shape correction, variable selection, determination of key variables, eigenvalue plots to determine the number and position of components, and finally resolution using factor analysis. Copyright © 2002 John Wiley & Sons, Ltd.
Mathematical modeling of titration curves
Authors: Morales Daniel A.
Published: October 2002

It has frequently been observed that the shapes of titration curves closely resemble those of inverse hyperbolic or trigonometric functions. Here we show that there exists not only a resemblance, but that, for simple titration reactions, we can derive expressions which represent the change in a solution property with the volume of titrant added, in terms of inverse hyperbolic or trigonometric functions. The general mathematical form of the expressions so obtained is then used to model these and other, more complicated titrations. Copyright © 2002 John Wiley & Sons, Ltd.
Asymmetric total synthesis of highly symmetric squalene‐derived cytotoxic polyethers
Authors: Morimoto Yoshiki , Kinoshita Takamasa , Iwai Toshiyuki
Published: October 2002

The efficient total synthesis of the cytotoxic meso polyether teurilene (1), rarely occurring in nature, was achieved through the effective combination of the concept of two‐directional synthesis and rhenium(VII) chemistry. In the key rhenium(VII)‐promoted syn oxidative cyclization reaction of the two‐directional substrate 16, trans‐syn diastereoselectivity (steric control) has been observed in contrast to our early observation of cis‐syn diastereoselectivities (chelation control) for bishomoallylic tertiary alcohols 24–27 possessing the neighboring tetrahydrofuran (THF) ring. This synthesis in only 10 steps from commercially available methyl tiglate is significantly shorter than the previous one requiring 25 steps. The total syntheses of four possible Cs symmetric (3 and 47–49) and one C2 symmetric (4) compounds for biogenetically squalene‐derived pentaTHF polyether, glabrescol, was also achieved in relatively few steps by taking advantage of its intrinsic symmetry and one‐ and two‐directional modes of double THF ring formations with vanadium catalyst, tert‐butyl hydroperoxide (TBHP), and trifluoroacetic acid (TFA). Thus, the meso structure 3 originally proposed by Jacobs et al. has been revised to the optically pure C2 symmetric structure 4 through its enantioselective total synthesis. Chirality 14:578–586, 2002.© 2002 Wiley‐Liss, Inc.
Synthesis and structure of poly(binaphthyl salen manganese complex) and its application to asymmetric epoxidation
Authors: Maeda Takeshi , Furusho Yoshio , Takata Toshikazu
Published: October 2002

Poly(binaphthyl salen manganese complex)es 3‐Mn were synthesized from a 3,3′‐diformylbinaphthol derivative, α,ω‐diamines, and Mn(OAc)2. Their helical structures were well‐supported by their IR, UV, and CD spectra. The catalysis of 3‐Mn in an asymmetric epoxidation was investigated. Chirality 14:587–590, 2002. © 2002 Wiley‐Liss, Inc.
Ligand distortion modes leading to increased chirality content of Katsuki‐Jacobsen catalysts
Authors: Lipkowitz Kenny B. , Schefzick Sabine
Published: October 2002

The “chirality content” of Katsuki‐Jacobsen epoxidation catalysts are computed with the Avnir continuous chirality measure (CCM). An assessment of Mn(salen) molecules from the Cambridge Structural Database shows there exist some variation in CCM and the chirality content for several triplet state complexes of these catalysts purported in the literature to be the active species show even larger CCM values. Several deformation modes were analyzed to examine how chirality content changes as catalyst distortion is induced. The deformations studied include in‐plane deformations, cup‐shaped puckering, ligand twisting motions, and step‐like deformations. Some distortions lead to increases of chirality while others lead to a decrease in chirality content. The most influential distortion modes that can be used for ligand design are twisting and step induction. Chirality 14:677–682, 2002. © 2002 Wiley‐Liss, Inc.
Radiation‐induced cavernous hemangiomas of the brain
Authors: Heckl Stefan , Aschoff Alfred , Kunze Stefan
Published: October 2002

INTRODUCTION

The induction of cavernomas as a consequence of brain irradiation was first suspected in 1994 and has been controversial since that time.

METHODS

Between 1986 and 2000, 189 cerebral cavernomas were diagnosed in the Neurosurgical Department of the University of Heidelberg; of those patients, 5 had received prior radiation therapy. The ages of these 5 patients were compared with those of the 184 others with naturally occuring cavernomas. In an examination of 40 patients with cavernomas occurring after radiation (the 5 mentioned above, plus 35 from the literature) the age distribution was investigated, and a possible relationship between radiation dosage and latency interval to diagnosis of cavernoma was examined.

RESULTS

Almost one in four of the patients under 15 years of age diagnosed with a cerebral cavernoma in the Neurosurgical Department of the University of Heidelberg had received prior radiation. In 40 patients with cavernomas and prior radiation (5 from Heidelberg, 35 from the literature), there was a clear accumulation in the age group of 10–19 years (50%). Most of those patients had received radiation in the first 10 years of life. The accumulation of cavernomas after radiation in childhood could not be explained by a greater frequency of radiation exposure in children compared to adults. In children up to 10 years of age at the time of radiation therapy, a dose of 3000 cGy and higher was followed by a shorter latency interval to incidence of cavernoma (P = 0.0018). In patients older than 10 years at the time of radiation, postradiation cavernomas only occurred when dosage was 3000 cGy or greater.

CONCLUSION

These results indicate a correlation between radiation and cavernoma, particularly in children under 10 years of age at the time of radiation therapy. In adults, cavernomas after radiation rarely occur, and then only after higher radiation dosages (3000 cGy or more). Cancer 2002;94:3285–91. © 2002 American Cancer Society.

DOI 10.1002/cncr.10596
Phase II trial of gemcitabine in advanced sarcomas
Authors: Okuno Scott , Edmonson John , Mahoney Michelle , Buckner Jan C. , Frytak Stephen , Galanis Evanthia
Published: October 2002

BACKGROUND

Care for patients with advanced sarcomas is mainly palliative. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine that has shown antitumor activity in several tumors. The aim of the current study was to determine the clinical activity of gemcitabine in patients with sarcomas.

METHODS

The authors evaluated gemcitabine in patients with histologically confirmed sarcomas; one prior exposure to chemotherapy treatment was allowed. Prior radiation was allowed if given to non‐indicator lesions. Treatment consisted of gemcitabine 1250 mg/m2 intravenously over 30 minutes, every week × three, cycles repeated q28 days.

RESULTS

Twenty nine of 30 patients were evaluable; one patient refused to initiate study treatment. The mean age was 50 years (range, 22‐81 years); 59% were male, and 35% had an Eastern Cooperative Oncology Group performance status of 0 (vs. 1 or 2). Patients were histologically classified as leiomyosarcoma (seven gastrointestinal, four retroperitoneal, two inferior vena caval, three of the extremity, and two uterine), synovial (two patients), malignant fibrous histiocytoma (two patients), fibrosarcoma (one patient), osteosarcoma (two patients), liposarcoma (one patient), hemangiosarcoma (one patient), or giant cell (one patient). Patients received an average of two cycles (range, one to eight). Eighty three percent of patients discontinued treatment due to progression and 14% due to toxicity/refusal. Hematologic toxicities ≥ Grade 3 were seen in 32% of patients and consisted of leukopenia and thrombocytopenia. Anorexia (Grade 1/2 in 6 patients, Grade 3 in 1 patient), nausea (Grade 1/2 in 7 patients, Grade 3 in 1 patient), and lethargy (Grade 1/2 in 19 patients) were the most frequently observed nonhematologic toxicities. One patient experienced Grade 3 edema and muscle infarction. A different patient experienced unexplained Grade 3 chest pain. One partial response was observed in a uterine leiomyosarcoma patient lasting at least three months. Overall response rate was 3% (95% confidence interval [CI]: 0‐15). Median time ‐to progression was 2.1 months (95% CI: 1.8–3.0).

CONCLUSIONS

The current gemcitabine regimen demonstrated acceptable levels of toxicity, but it failed to produce the number of responses needed to justify expansion of the current study. This regimen is not recommended for advanced sarcomas. Cancer 2002;94:3225–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10602
A natural history of melanomas and dysplastic nevi
Authors: Tucker Margaret A. , Fraser Mary C. , Goldstein Alisa M. , Struewing Jeffery P. , King Mary A. , Crawford John T. , Chiazze Ellen A. , Zametkin Deborah P. , Fontaine Laura S. , Clark Wallace H.
Published: October 2002

BACKGROUND

Few long‐term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes.

METHODS

Thirty‐three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups.

RESULTS

All the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early.

CONCLUSIONS

The melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families. Cancer 2002;94:3192–209. © 2002 American Cancer Society.

DOI 10.1002/cncr.10605
GLI3 is not mutated commonly in sporadic medulloblastomas
Authors: Erez Ayelet , Ilan Tsafra , Amariglio Ninette , Muler Inna , Brok‐Simoni Frida , Rechavi Gideon , Izraeli Shai
Published: October 2002

BACKGROUND

Medulloblastoma is a malignant, invasive embryonic tumor of the cerebellum. Sonic hedgehog (SHH) is a secreted glycoprotein that has a major role in the developing cerebellum. Activation of the SHH pathway resulting from mutations in the PATCH gene, which is an inhibitor of the pathway, are associated with hereditary and sporadic medulloblastomas. The GLI3 protein is another negative regulator of SHH signaling. The authors hypothesized that mutations in GLI3 may be associated with meduloblastomas.

METHODS

The authors describe a patient with hereditary Greig syndrome, which was caused by mutations in GLI3, and medulloblastoma. Another such patient was described in the literature. They also sequenced the GLI3 gene, including all exon‐intron boundaries, in an additional 12 sporadic medulloblastomas.

RESULTS

The authors detected a new nonsense germline mutation in a child with Greig syndrome and medulloblastoma. This mutation generates a stop codon in position 809 of GLI3 that has been predicted to result in massive truncation of the protein. Several new polymorphisms, but no tumor‐associated mutations, were found in sporadic tumors.

CONCLUSIONS

Gli3 is mutated rarely in medulloblastoma. Cancer 2002;95:28–31. © 2002 American Cancer Society.

DOI 10.1002/cncr.10642
Changes in presentation and survival of head and neck carcinomas in Northeastern Italy, 1975–1998
Authors: Barzan Luigi , Talamini Renato , Franchin Gianni , Vaccher Emanuela , Politi Doriano , Minatel Emilio , Gobitti Carlo
Published: October 2002

BACKGROUND

During the last 20 years, survival rates of head and neck carcinoma patients in the United States and Europe have plateaued. To determine the factors that can reduce mortality rates, we examined changes in clinical presentation and survival rates across 24 years of treatment of head and neck carcinoma patients.

METHODS

A retrospective study of patients with head and neck carcinoma was conducted from January 1, 1975, to December 31, 1998. We identified 2143 eligible patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx. Changes in gender, clinical stage, and therapy were evaluated separately for each site of cancer across five consecutive periods. Probability of dying and overall survival rates were estimated. Odds ratios (ORs) and hazard ratios were calculated.

RESULTS

An increase in T1 versus T2 or higher stage carcinoma was more probable for the oral cavity and larynx (OR = 4.1 and 3.0, respectively) in the last versus the earliest period. An increase in radical treatments was more probable for carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx (10.2, 34.8, 12.5, and 2.1‐fold, respectively) in the last versus the earliest period. A decreasing trend of probability of dying from the first head and neck carcinoma during the 1970s versus the 1990s was found. The overall survival rates at 5 years was 32% in 1975–1978 versus 51% in 1989–1993.

CONCLUSIONS

In contrast with survival rates in the United States and Europe, our findings show a significant increase in overall survival rates during the last 20 years. This increase is attributable to changes in diagnostic‐therapeutic approaches and to early consultation with a physician for symptoms arising in the head and neck region. Cancer 2002;95:540–52. © 2002 American Cancer Society.

DOI 10.1002/cncr.10682
Follicular thyroid carcinoma
Authors: Chow Sin‐Ming , Law Stephen C. K. , Mendenhall William M. , Au Siu‐Kie , Yau Stephen , Yuen Kam‐Tong , Law Chi‐Ching , Lau Wai‐Hon
Published: October 2002

BACKGROUND

The objective of this study was to investigate the patterns of recurrence, various prognostic factors, and the role of radioiodine in the treatment of patients with follicular thyroid carcinoma (FTC).

METHODS

The clinical outcomes of 215 patients with FTC who were treated at a single institution were analyzed retrospectively. The mean follow‐up was 10.8 years.

RESULTS

The actuarial rates of cause specific survival (CSS), locoregional (LR) control, and freedom from distant metastasis (DM) at 10 years were 81%, 83%, and 72.3%, respectively. The independent prognostic factors for survival were metastasis at presentation (relative risk [RR], 47.7), radioiodine (RAI) treatment (RR, 0.25), extrathyroidal extension (RR, 3.8), and the postoperative absence of macroscopic disease in the neck region (RR, 0.06). In patients who were treated with RAI, both the LR failure rate (RR, 0.24) and the mortality rate (RR, 0.25) were reduced to about 25%. Subgroup analysis revealed that RAI improved the survival of patients with DM at presentation (RR, 0.17) and improved the LR control rate in patients who had no DM at presentation (RR, 0.13). For patients who underwent total thyroidectomy with negative resection margins, RAI significantly reduced the rate of LR recurrence (RR, 0.05). Patients with the minimally invasive type of FTC had a good prognosis. The 10‐year rates for CSS, LR control, and freedom from DM were 97.6%, 100%, and 90.6%, respectively. The prognosis of patients with frankly invasive FTC was much poorer. The 10‐year rates for CSS, LR control, and freedom from DM were 66.7%, 100%, and 45%, respectively.

CONCLUSIONS

RAI is an effective treatment for patients with FTC. It was associated with improved survival rates and fewer recurrences. Cancer 2002;95:488–98. © 2002 American Cancer Society.

DOI 10.1002/cncr.10683
Plasma osteopontin
Authors: Hotte Sebastien J. , Winquist Eric W. , Stitt Larry , Wilson Sylvia M. , Chambers Ann F.
Published: October 2002

BACKGROUND

Osteopontin (OPN) is a secreted glycoprotein that is detectable in human body fluids. Its increased expression has been found in many malignancies, and a stimulatory effect on human prostate carcinoma cells in vitro has been demonstrated. Plasma OPN levels have been associated with tumor burden and survival in patients with metastatic breast carcinoma. The authors explored these associations in men with hormone‐refractory prostate carcinoma (HRPC).

METHODS

Plasma samples from 100 men with HRPC were collected. OPN was measured using an antigen‐capture enzyme‐linked immunosorbent assay technique. Multivariable analyses were performed to identify predictors of OPN and survival.

RESULTS

At the time of OPN sampling, the median patient age was 73 years (range, 50–86 years), and 92% of patients had metastases. The median plasma OPN level was 198.5 ng/mL (range, 15.0–2363.0 ng/mL), the median prostate specific antigen level was 67.8 μg/L (range, 0.1–7550.0 μg/L), and the median survival was 13.7 months. OPN plasma levels were higher in patients with versus patients without bone metastases (P = 0.024). Multivariable modeling demonstrated an independent association of the OPN level with alkaline phosphatase, hemoglobin, and creatinine levels. The log‐transformed OPN level (hazard ratio [HR], 2.38; P < 0.0001), performance status (HR, 2.43; P = 0.007), and a history of prior radiotherapy for localized prostate carcinoma (HR, 0.48; P = 0.0229) were independent predictors of survival in a Cox multivariate model.

CONCLUSIONS

In this study, in men with established HRPC, the plasma OPN level was associated with the presence of metastases to bone and with other measures of tumor burden, and it was correlated independently and negatively with survival. Cancer 2002;95:506–12. © 2002 American Cancer Society.

DOI 10.1002/cncr.10709
Severe periorbital edema secondary to STI571 (Gleevec)
Authors: Esmaeli Bita , Prieto Victor G. , Butler Charles E. , Kim Stella K. , Ahmadi M. Amir , Kantarjian Hagop M. , Talpaz Moshe
Published: October 2002

STI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr‐abl, c‐kit, and platelet‐derived growth factor receptor tyrosine kinases. Mild periorbital edema has been noted as a common side effect in Phase I and II trials of this drug for the treatment of patients with chronic myelogenous leukemia and gastrointestinal stromal tumors. The authors report the case of male patient age 63 years who developed severe periorbital edema after treatment with STI571 for chronic myelogenous leukemia. His edema was severe enough to cause visual obstruction due to lower eyelid festoons that ultimately required surgical debulking. Histopathologic analysis of specimens of the excised upper and lower eyelid tissue revealed dermal dendrocytes that expressed the platelet‐derived growth factor receptor and c‐kit tyrosine kinases, suggesting a possible role for dermal dendrocytes in the development of this toxic effect. Cancer 2002;95:881–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10729
β1‐integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen‐activated protein kinase dependent pathway
Authors: Zhang Hao , Ozaki Iwata , Mizuta Toshihiko , Matsuhashi Sachiko , Yoshimura Tohru , Hisatomi Akitaka , Tadano Jutaro , Sakai Takahiro , Yamamoto Kyosuke
Published: October 2002

BACKGROUND

β1‐integrin modulates cellular phenotype by mediating signals from the extracellular matrix (ECM). Although overexpression of integrin molecules in hepatocellular carcinoma (HCC) has been reported, the role of overexpressed β1‐integrin in the disease process of HCC is not fully understood. The authors investigated the effects of β1‐integrin on apoptosis in hepatoma cells.

METHODS

Human hepatoma cell lines HepG2, Huh7, and HLE were stably transfected with full‐length β1‐integrin. Cells underwent apoptosis induced by chemotherapeutic reagents, including cis‐platinum (II)‐diammine dichloride, etoposide, and docetaxel. Cell survival and intracellular signaling pathways dependent on β1‐integrin‐mediated apoptosis effects were analyzed by treating cells with PD98059 (ERK inhibitor), SB203580 (p38MAP kinase inhibitor), wortmannin (phosphatidyl inositol‐3‐kinase inhibitor), and herbimycin A (tyrosine kinase inhibitor).

RESULTS

All three hepatoma cell lines overexpressing β1‐integrin were protected from apoptosis induced by chemotherapeutic reagents, whereas parental or mock transfected cells were not. Treatment with PD98059 or SB203580 abolished the protective effect on apoptosis in cells overexpressing β1‐integrin. Neither herbimycin nor wortmannin blocked the protective effects of β1‐integrin overexpression.

CONCLUSIONS

These data suggest that overexpression of β1‐integrin confers resistance to apoptosis in hepatoma cells via a MAP kinase dependent pathway. β1‐integrin mediated signaling from the ECM in HCC cells may contribute to chemotherapy resistance. Cancer 2002;95:896–906. © 2002 American Cancer Society.

DOI 10.1002/cncr.10751
Quantitative ultrastructural analysis of glycine‐ and γ‐aminobutyric acid‐immunoreactive terminals on trigeminal α‐ and γ‐motoneuron somata in the rat
Authors: Bae Yong Chul , Choi Byung Ju , Lee Maan Gee , Lee Hyo Jeong , Park Kuk Pil , Zhang Li Fen , Honma Shiho , Fukami Hideyuki , Yoshida Atsushi , Ottersen Ole Petter , Shigenaga Yoshio
Published: October 2002

Detailed knowledge of the inhibitory input to trigeminal motoneurons is needed to understand better the central mechanisms of jaw movements. Here a quantitative analysis of terminals contacting somata of jaw‐closing (JC) and jaw‐opening (JO) α‐motoneurons, and of JC γ‐motoneurons, was performed by use of serial sectioning and postembedding immunogold cytochemistry. For each type of motoneuron, the synaptic boutons were classified into four groups, i.e., immunonegative boutons or boutons immunoreactive to glycine only, to γ‐aminobutyric acid (GABA) only, or to both glycine and GABA. The density of immunolabeled boutons was much higher for the α‐ than for the γ‐motoneurons. In the α‐motoneuron populations, the immunolabeled boutons were subdivided into one large group of boutons containing glycine‐like immunoreactivity only, one group of intermediate size harboring both glycine‐ and GABA‐like immunoreactivity, and a small group of boutons containing GABA‐like immunoreactivity only. The percentage of immunolabeled boutons was higher for JC than JO α‐motoneurons, the most pronounced difference being observed for glycine‐like immunoreactivity. In contrast, on the somatic membrane of γ‐motoneurons, the three types of immunoreactive bouton occurred at similar frequencies. These results indicate that trigeminal motoneurons are strongly and differentially controlled by premotoneurons containing glycine and/or GABA and suggest that these neurons play an important role for the generation of masticatory patterns. J. Comp. Neurol. 442:308–319, 2002. © 2002 Wiley‐Liss, Inc.
Developmental expression of monoamine oxidases A and B in the central and peripheral nervous systems of the mouse
Authors: Vitalis Tania , Fouquet Coralie , Alvarez Chantal , Seif Isabelle , Price David , Gaspar Patricia , Cases Olivier
Published: October 2002

Monoamine oxidases A (MAOA) and B (MAOB) are key players in the inactivation pathway of biogenic amines. Their cellular localization has been well established in the mature brain, but nothing is known concerning the localization of both enzymes during development. We have combined in situ hybridization and histochemistry to localize MAOA and MAOB in the developing nervous system of mice. Our observations can be summarized as five key features. (1) MAOA is tightly linked to catecholaminergic traits. MAOA is expressed in all noradrenergic and adrenergic neurons early on, and in several dopaminergic cell groups such as the substantia nigra. MAOA is also expressed in all the neurons that display a transient tyrosine hydroxylase expression in the brainstem and the amygdala and in neurons with transient dopamine‐β‐hydroxylase expression in the cranial sensory ganglia. (2) MAOA and MAOB are coexpressed in the serotoninergic neurons of the raphe from E12 to P7. During postnatal life, MAOA expression declines, whereas MAOB expression remains stable. (3) MAOA is transiently expressed in the cholinergic motor nuclei of the hindbrain, and MAOB is expressed in the forebrain cholinergic neurons. (4) MAOA‐ and MAOB‐expressing neurons are also detected in structures that do not contain aminergic neurons, such as the thalamus, hippocampus, and claustrum. (5) Starting at birth, MAOB expression is found in a variety of nonneuronal cells, the choroid plexus, the ependyma, and astrocytes. These localizations are of importance for understanding the effects of monoaminergic transmission during development. J. Comp. Neurol. 442:331–347, 2002. © 2002 Wiley‐Liss, Inc.
Orcokinin peptides in developing and adult crustacean stomatogastric nervous systems and pericardial organs
Authors: Li Lingjun , Pulver Stefan R. , Kelley Wayne P. , Thirumalai Vatsala , Sweedler Jonathan V. , Marder Eve
Published: October 2002

The orcokinins are a family of neuropeptides recently isolated from several crustacean species. We found orcokinin‐like immunoreactivity in the stomatogastric nervous systems and pericardial organs of three decapod crustacean species, Homarus americanus, Cancer borealis, and Panulirus interruptus. The neuropil of the stomatogastric ganglion was stained in adults of all three species as well as in embryonic and larval H. americanus. In H. americanus, the somata giving rise to this projection were found in the inferior ventricular nerve. Matrix‐assisted laser desorption/ionization mass spectrometry mass profiling and sequencing with postsource decay led to the identification of six different orcokinin family peptides, including those previously described in other decapods and two novel shorter peptides. Application of exogenous [Ala13]orcokinin to the stomatogastric ganglion of H. americanus resulted in changes in the pyloric rhythm. Specifically, the number of lateral pyloric (LP) neuron spikes/burst decreased, and the phase of firing of the pyloric neurons was altered. Together, these data indicate that the orcokinins are likely to function as modulators of the crustacean stomatogastric ganglion. J. Comp. Neurol. 444:227–244, 2002. © 2002 Wiley‐Liss, Inc.
Vesicular glutamate transporter DNPI/VGLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurons of the rat medulla
Authors: Stornetta Ruth L. , Sevigny Charles P. , Schreihofer Ann M. , Rosin Diane L. , Guyenet Patrice G.
Published: October 2002

The main source of excitatory drive to the sympathetic preganglionic neurons that control blood pressure is from neurons located in the rostral ventrolateral medulla (RVLM). This monosynaptic input includes adrenergic (C1), peptidergic, and noncatecholaminergic neurons. Some of the cells in this pathway are suspected to be glutamatergic, but conclusive evidence is lacking. In the present study we sought to determine whether these presympathetic neurons express the vesicular glutamate transporter BNPI/VGLUT1 or the closely related gene DNPI, the rat homolog of the mouse vesicular glutamate transporter VGLUT2. Both BNPI/VGLUT1 and DNPI/VGLUT2 mRNAs were detected in the medulla oblongata by in situ hybridization, but only DNPI/VGLUT2 mRNA was present in the RVLM. Moreover, BNPI immunoreactivity was absent from the thoracic spinal cord lateral horn. DNPI/VGLUT2 mRNA was present in many medullary cells retrogradely labeled with Fluoro‐Gold from the spinal cord (T2; four rats). Within the RVLM, 79% of the bulbospinal C1 cells contained DNPI/VGLUT2 mRNA. Bulbospinal noradrenergic A5 neurons did not contain DNPI/VGLUT2 mRNA. The RVLM of six unanesthetized rats subjected to 2 hours of hydralazine‐induced hypotension contained tenfold more c‐Fos‐ir DNPI/VGLUT2 neurons than that of six saline‐treated controls. c‐Fos‐ir DNPI/VGLUT2 neurons included C1 and non‐C1 neurons (3:2 ratio). In seven barbiturate‐anesthetized rats, 16 vasomotor presympathetic neurons were filled with biotinamide and analyzed for the presence of tyrosine hydroxylase immunoreactivity and/or DNPI/VGLUT2 mRNA. Biotinamide‐labeled neurons included C1 and non‐C1 cells. Most non‐C1 (9/10) and C1 presympathetic cells (5/6) contained DNPI/VGLUT2 mRNA. In conclusion, DNPI/VGLUT2 is expressed by most blood pressure‐regulating presympathetic cells of the RVLM. The data suggest that these neurons may be glutamatergic and that the C1 adrenergic phenotype is one of several secondary phenotypes that are differentially expressed by subgroups of these cells. J. Comp. Neurol. 444:207–220, 2002. © 2002 Wiley‐Liss, Inc.
Skin blood vessels are simultaneously innervated by sensory, sympathetic, and parasympathetic fibers
Authors: Ruocco Isabella , Cuello A. Claudio , Parent André , Ribeiro‐Da‐Silva Alfredo
Published: October 2002

Despite the known major role of skin blood vessel innervation in blood flow control, particularly in disease, little information on the co‐innervation of blood vessels by sensory and autonomic fibers and the relationships of these fibers to one another is available. To fill this gap, we performed a light and electron microscopic analysis of the innervation of skin vessels by sensory and autonomic fibers by using the rat and monkey lower lips as a model. In rats, double‐labeling immunocytochemistry revealed that combinations of fibers immunoreactive for substance P (SP) and dopamine‐β‐hydroxylase (DβH), SP and vesicular acetylcholine transporter (VAChT), as well as DβH and VAChT occurred only around blood vessels in the lower dermis. All fiber types travelled in parallel and in close proximity to one another. In the upper dermis, blood vessels were innervated by SP‐containing fibers only. Although nerve terminals displayed synaptic vesicles, synaptic specializations were never observed, suggesting that, in this territory, these fibers do not establish synaptic contacts. Quantification of the distance between the various immunoreactive terminals and their presumptive targets (smooth muscle cells and endothelial cells) revealed that both sympathetic and parasympathetic fibers were significantly closer to the endothelial cell layer and smooth muscle cells compared with sensory fibers. In monkeys, double‐labeling immunocytochemistry was performed for SP‐DβH and SP‐VAChT only. The results obtained are similar to those found in rats; however, the fiber density was greater in monkeys. Our findings suggest that the regulation of skin microcirculation might be the result of the coordinated functions of sensory and autonomic fibers. J. Comp. Neurol. 448:323–336, 2002. © 2002 Wiley‐Liss, Inc.
Cocaine‐ and amphetamine‐regulated transcript peptide projections in the ventral midbrain: Colocalization with γ‐aminobutyric acid, melanin‐concentrating hormone, dynorphin, and synaptic interactions with dopamine neurons
Authors: Dallvechia‐Adams Stephanie , Kuhar Michael J. , Smith Yoland
Published: October 2002

To date, cocaine‐ and amphetamine‐regulated transcript (CART) peptides have been found to influence feeding, locomotor activity, and conditioned place preference. A common brain structure that could mediate these effects is the ventral tegmental area (VTA). For a better understanding of the anatomical substrates that might underlie CART peptides' role in these behaviors, we performed a series of experiments to elucidate the source, synaptic connectivity, and neurochemical content of CART peptide‐immunoreactive (CARTir) terminals in the rat VTA. Double‐labeling immunofluorescence revealed that approximately 15% of CARTir terminals in the VTA contain the hypothalamic neuropeptide, melanin‐concentrating hormone (MCH). Furthermore, CART peptides were also found to colocalize with GABA and, to a small extent, with dynorphin in nerve terminals in both the VTA and the substantia nigra (SN). In the VTA, CARTir terminals form both symmetric and asymmetric synapses onto dopaminergic and nondopaminergic distal dendrites, suggesting that various sources contribute to this innervation. About 30% of CARTir terminals in the VTA and only 15% in the SN appose or form synaptic contact with DA neurons, which support our previous data showing that GABAergic basal ganglia output neurons in the substantia nigra pars reticulata (SNr) receive strong CARTir input from the accumbens core. Results of these studies suggest that the most significant behavioral states influenced by CART peptides, feeding and locomotion, may be mediated by direct and/or indirect modulation of VTA dopaminergic neuronal activity. J. Comp. Neurol. 448:360–372, 2002. © 2002 Wiley‐Liss, Inc.
Pattern of synaptic excitation and inhibition upon direction‐selective retinal ganglion cells
Authors: Jeon Chang‐Jin , Kong Jee‐Hyun , Strettoi Enrica , Rockhill Rebecca , Stasheff Steven F. , Masland Richard H.
Published: October 2002

The distributions of excitatory and inhibitory synapses upon the dendritic arbor of a direction‐selective retinal ganglion cell were compared by triple‐labeling techniques. The dendrites were visualized by confocal microscopy after injection of Lucifer yellow. Excitatory inputs from bipolar cells were located by using antibodies against kinesin II, a component of synaptic ribbons. Inhibitory inputs were identified by antibodies against γ‐aminobutyric acid‐A receptors. The combined images were examined by visual inspection and by formal, automated analyses, in a search for anisotropies that might contribute to a directional preference of the ganglion cell. Within the limits of our analysis, none was found. If an anatomic specialization underlies direction selectivity, it appears to lie in the geometry and spatial positioning of the neurons afferent to the ganglion cell and/or the microcircuitry among its afferent synapses. J. Comp. Neurol. 449:195–205, 2002. © 2002 Wiley‐Liss, Inc.