bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Imaging
Authors: Prost Robert W.
Published: October 2003

Imaging of materials that contain nuclei of nonzero spin values has become a valuable tool in science, medicine, and industry. The principal use of MRI is to create an image of the distribution of certain physical properties of a substance, whether in the fluid‐filled rock surrounding an oil well, soil, food‐processing, industrial process control or a human subject. These physical properties imaged include the chemistry of the material, its fluidity, its interactions with other materials in the molecular‐level neighborhood, and even the flow of liquids within the object. Magnetic resonance phenomena occur on a timescale that is short relative to many chemical reactions and can often be used to investigate the kinetics of chemical reactions.

Many different elements are amenable to investigation by magnetic resonance, but the sensitivity of MR is poor. As a result of this insensitivity, magnetic resonance is not suited to detecting of chemical moities of less than millimolar quantities. For the same reason, gases are largely unsuitable to investigation by magnetic resonance, except for hyperpolarized gases3He and129Xe.

All solid or liquid objects, that bear suitable nuclei can be imaged. However, spins within solid materials lose their signal on a very short timescale. This brevity of signal lifetime makes imaging quite difficult, yet not impossible.

Examples of nuclei that bear a magnetic moment, or nonzero spin include hydrogen, helium‐3, xenon‐129, phosphorus, lithium, fluorine, carbon‐13 and sodium‐23.

An important and recent use of the MR phenomenon is in medical imaging. The reason for the success of MRI in medical imaging is fourfold. The first is the abundance of hydrogen in the human body. Hydrogen nuclei in the brain are about 70 Molar in concentration which is much higher than any other material that can be detected by NMR. The second is that the hydrogen is distributed in the organs in a way which allows using the MR signal to create images. The third is that imaging of hydrogen produces exquisitely detailed images of internal organ structure. The fourth is the functional data that can be extracted. These data include molecular diffusion, distribution of chemical moieties, flow, flow in the capillary bed, oxygen utilization, magnetization transfer rates, and disruption of the blood–brain barrier.

Basic MRI physics, imaging processing and k‐space, endogenous image contract and other mechanisms are discussed.
Anticipation and repeat expansion in bipolar disorder
Authors: O'Donovan Michael , Jones Ian , Craddock Nick
Published: October 2003

Anticipation is the phenomenon whereby a disease becomes more severe and/or presents with earlier onset as it is transmitted down through generations of a family. The only known mechanism for true anticipation is a class of mutations containing repetitive sequences exemplified by the pathogenic trinucleotide repeat. Studies of bipolar disorder (BPD) are consistent with the presence of anticipation and, by inference, the possibility that trinucleotide repeats contribute to this disorder, although it is possible that these data are the result of methodological problems. On the assumption that anticipation in BPD may be real, several surveys of the genome of BPD probands for large trinucleotide repeats have been conducted, as have studies of many repeat‐containing candidate genes. No pathogenic triplet repeat has yet been unambiguously implicated. © 2003 Wiley‐Liss, Inc.
Family, twin, and adoption studies of bipolar disorder
Authors: Smoller Jordan W. , Finn Christine T.
Published: October 2003

Family, twin, and adoption studies have been essential in defining the genetic epidemiology of bipolar disorder over the past several decades. Family studies have documented that first‐degree relatives of affected individuals have an excess risk of the disorder, while twin studies (and to a lesser extent, adoption studies) suggest that genes are largely responsible for this familial aggregation. We review these studies, including the magnitude of familial risk and heritability estimates, efforts to identify familial subtypes of bipolar disorder, and the implications of family/genetic data for validating nosologic boundaries. Taken together, these studies indicate that bipolar disorder is phenotypically and genetically complex. © 2003 Wiley‐Liss, Inc.
The neurobiology of bipolar disorder
Authors: Berns Gregory S. , Nemeroff Charles B.
Published: October 2003

The neurobiology of bipolar disorder is reviewed. Bipolar disorder is associated with alterations in central nervous system (CNS) function from the level of large‐scale brain circuits to intracellular signal transduction mechanisms. Because of the broad spectrum over which these abnormalities appear, the causative effects are most likely present in the lowest common denominator of all of these systems. Current evidence points to subtle alterations in signal transduction that reverberate downstream both intra‐ and extracellularly to produce the symptoms of bipolar disorder. © 2003 Wiley‐Liss, Inc.
Fortschritte bei der Synthese anorganischer Nanoröhren und Fulleren‐artiger Nanopartikel
Authors: Tenne Reshef
Published: October 2003

Wie Graphit sind Nanopartikel aus anorganischen Verbindungen mit zweidimensionaler lamellarer Struktur wie MoS2 gegen Faltung instabil und können daher Nanoröhren und Fulleren‐artige Strukturen, auch anorganische Fullerene oder IFs genannt, liefern. Für solche Nanomaterialien wurde eine Reihe von Anwendungen vorgeschlagen. So ließen sich IF‐WS2‐Nanopartikel als festes Schmiermittel und als Teil tribologischer Oberflächen nutzen. Weitere Anwendungen von IFs für Fasern mit hoher Zugfestigkeit, als Wasserstoffspeicher, für wiederaufladbare Batterien, in der Katalyse und in der Nanotechnologie werden diskutiert. Dieser Kurzaufsatz beleuchtet einige der neuesten Entwicklungen bei der Synthese anorganischer Nanoröhren und Fulleren‐artiger Strukturen. Des Weiteren werden strukturelle Gesichtspunkte und Eigenschaften von IFs kurz diskutiert, in denen sie sich von den lamellaren Materialien als solchen unterscheiden.
Synthetic Expanded Porphyrin Chemistry
Authors: Sessler Jonathan L. , Seidel Daniel
Published: October 2003

Expanded porphyrins are synthetic analogues of the porphyrins, and differ from these and other naturally occurring tetrapyrrolic macrocycles by containing a larger central core with a minimum of 17 atoms, while retaining the extended conjugation features that are a hallmark of these quintessential biological pigments. The result of core expansion is to produce systems with novel spectral and electronic features, interesting and, often unprecedented, cation‐coordination properties, and, in many cases, an ability to bind anions in certain protonation states. Also adding to the appeal of expanded porphyrins is their central role in addressing issues of aromaticity. In many cases, they also display structural features, such as decidedly nonplanar “figure‐eight” motifs, that have no antecedents in the chemistry of porphyrins or related macrocyclic compounds. In this Review, the various synthetic approaches now being employed to produce expanded porphyrins as well as their various applications‐related aspects are discussed.
Cover Picture: Competitive Binding Assays Made Easy with a Native Marker and Mass Spectrometric Quantification (Angew. Chem. Int. Ed. 42/2003)
Authors: Höfner Georg , Wanner Klaus Theodor
Published: October 2003

Mass spectrometric methods are on the march in competitive binding studies. In pharmacological research these studies are widely used to characterize ligand–target interactions. However, they usually require the use of radioligands. Now, with the aid of mass spectrometry, it is possible to use native markers instead of radioligands. This method and its use in a binding study on dopamine D1‐receptors are described in the Communication by G. Höfner and K. T. Wanner on page 5235 ff.
Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki‐67 expression
Authors: Uchikawa Junko , Shiozawa Tanri , Shih Hsien‐Chang , Miyamoto Tsutomu , Feng Yu‐Zhen , Kashima Hiroyasu , Oka Kenji , Konishi Ikuo
Published: October 2003

BACKGROUND

To examine the steroid hormone dependent growth mechanism of human endometrial hyperplasia and carcinoma, expression levels of steroid receptor cofactors, such as coactivators (steroid receptor coactivator 1 [SRC‐1] and p300/cyclic AMP‐response element‐binding protein (p300/CBP]) and corepressors (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and thyroid‐hormone receptors [SMRT]), were investigated.

METHODS

The expression levels of cofactors were examined immunohistochemically using 20 samples of normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant endometria and were compared with the expression levels of estrogen receptor (ER), progesterone receptor (PR), and a proliferation marker, Ki‐67.

RESULTS

In samples of normal endometria, the expression of coactivators was observed diffusely in glandular cells in the proliferative phase, with a mean positivity index (PI) of 81.8 for SRC‐1 and 91.3 for p300/CBP, whereas expression levels decreased in endometrial hyperplasia (PI: SRC‐1, 58.9; p300/CBP, 83.8) and endometrial carcinoma (PI: SRC‐1, 45.0; p300/CBP, 55.4). In endometrial hyperplasia, there was a significant correlation between the expression of ER and SRC‐1 or p300/CBP. In contrast, there were no significant statistical or topologic correlations between the expression of coactivators and the expression of ER/PR in endometrial carcinoma. The expression of corepressors generally was limited, except for elevated expression of NCoR in endometrial hyperplasia (PI, 23.8).

CONCLUSIONS

The current study showed that expression levels of the steroid receptor coactivators SRC‐1 and p300/CBP were reduced in endometrial carcinoma compared with normal and hyperplastic endometrium. In addition, topologic coexpression of both coactivators and ER/PR was lost in endometrial carcinoma. Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR. Cancer 2003. © 2003 American Cancer Society.
Occult “micrometastases” in ductal carcinoma in situ
Authors: Weaver Donald L.
Published: October 2003

Sentinel lymph node biopsy is frequently associated with identification of micrometastatic tumor deposits. The clinical relevance of identifying micrometastases in breast cancer must be evaluated in the statistical context of the lymph node evaluation strategy and the likelihood of missing a metastasis of similar size.

See also pages 2105–13.
Vascular endothelial growth factor is associated with the efficacy of endocrine therapy in patients with advanced breast carcinoma
Authors: Manders Peggy , Beex Louk V. A. M. , Tjan‐Heijnen Vivianne C. G. , Span Paul N. , Sweep C. (Fred) G. J.
Published: October 2003

BACKGROUND

Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with a poor prognosis in patients with primary breast carcinoma. In the current study, the authors investigated whether there was an association between VEGF levels in tumor tissues and response rates to first‐line, systemic therapy in patients with advanced breast carcinoma.

METHODS

In 172 tumors from patients with primary breast carcinoma who developed distant metastases during follow‐up, cytosolic levels of VEGF were measured using a quantitative enzyme‐linked immunosorbent assay. Patients received either endocrine therapy (n = 96) or chemotherapy (n = 76) as first‐line treatment after they were diagnosed with advanced disease.

RESULTS

In univariate logistic regression analysis for response to endocrine therapy in 96 patients, an increasing level of VEGF, as a log‐transformed, continuous variable, was correlated with a poor rate of response (P = 0.043). In multivariate analysis, a significantly lower rate of response to first‐line endocrine therapy was found for patients who had high VEGF levels compared with patients who had low VEGF levels (P = 0.025). Similar results were found for the subgroup of 82 patients who received tamoxifen (P = 0.011). An association of VEGF with response to first‐line endocrine therapy was found in addition to a predictive impact for estrogen receptor/progesterone receptor status (P = 0.027). VEGF levels did not predict the rate of response to first‐line chemotherapy.

CONCLUSIONS

The results demonstrated that the level of VEGF affects response to endocrine therapy independent of steroid hormone receptor status and may help to refine further the indication for this treatment in individual patients. Further studies are warranted to explain this underlying resistance to endocrine therapy. Cancer 2003. © 2003 American Cancer Society.
Intraarterial cisplatin with intravenous paclitaxel and ifosfamide as an organ‐preservation approach in patients with paranasal sinus carcinoma
Authors: Papadimitrakopoulou Vassiliki A. , Ginsberg Lawrence E. , Garden Adam S. , Kies Merrill S. , Glisson Bonnie S. , Diaz Eduardo M. , Clayman Gary , Morrison William H. , Liu Diane D. , Blumenschein George , Lippman Scott M. , Schommer Donald , Gillenwater Ann , Goepfert Helmuth , Hong Waun K.
Published: October 2003

BACKGROUND

The objectives of this study were to determine the efficacy, organ‐preservation rate, and safety of intraarterial (IA) cisplatin in combination with intravenous paclitaxel and ifosfamide in patients with locally advanced carcinoma of the paranasal sinuses who required orbital exenteration or major craniofacial resection for complete tumor resection.

METHODS

Patients were treated with intravenous paclitaxel (135 mg/m2) on Day 1, ifosfamide (1000 mg/m2) on Days 1–3, sodium mercaptoethanesulfonate (600 mg/m2) on Days 1–3, and IA cisplatin (100 mg/m2) on Day 1 every 21 days.

RESULTS

Of 24 study participants, 20 patients received at least 1 course of IA cisplatin, 1 patient had an early death, and 19 patients were evaluable for response. Five of those 19 patients (26%) achieved a complete response (CR), 6 patients (32%) achieved a partial response, and 8 patients (42%) had stable disease or developed progressive disease. Eye‐sparing surgery followed by radiotherapy (RT) was feasible in 7 of 24 patients, RT was offered to only 7 patients, whereas 3 patients received chemotherapy and RT, 2 patients refused further therapy, 3 patients underwent craniofacial resection with orbitectomy, and 1 patient was treated systemically for metastatic disease. At the completion of treatment, 14 of 23 patients (61%) with locally advanced disease were disease free, and the orbit was preserved in 21 of 24 patients (88%). The overall survival, progression‐free survival, and disease‐free survival rates at 2 years were 60%, 50%, and 84%, respectively. Toxicity was substantial, with two patients experiencing cerebrovascular ischemia (one transient and one cerebrovascular accident) and three patients experiencing cranial neuropathy, which was reversible in two patients.

CONCLUSIONS

Despite the encouraging organ‐preservation rate, the approach studied resulted in substantial toxicity, and more effective adjunctive therapy is needed. Alternative approaches, including the integration of targeted therapy agents in induction chemotherapy regimens followed by concomitant chemotherapy and RT or eye‐sparing surgery, need further exploration. Cancer 2003. © 2003 American Cancer Society.
Definitive radiotherapy alone or combined with a planned neck dissection for squamous cell carcinoma of the pharyngeal wall
Authors: Hull Matthew C. , Morris Christopher G. , Tannehill Scott P. , Werning John W. , Amdur Robert J. , Hinerman Russell W. , Villaret Douglas B. , Mendenhall William M.
Published: October 2003

BACKGROUND

In the current study,the authors analyzed the results of definitive radiotherapy for squamous cell carcinoma of the pharyngeal wall.

METHODS

Between 1964 and 2000, 148 patients were treated with definitive radiotherapy. All patients had a 2‐year minimum follow‐up.

RESULTS

The following 5‐year rates of local and ultimate local control were obtained: T1 disease, 93% and 93%; T2 disease, 82% and 87%; T3 disease, 59% and 61%; and T4 disease, 50% and 50%, respectively. Multivariate analysis revealed that twice‐daily fractionation (P= 0.0009), American Joint Committee on Cancer Stage I–II disease (P= 0.0051), and oropharyngeal primary site (P= 0.0193) were associated with improved locoregional control. The following 5‐year absolute and cause‐specific survival rates were obtained: Stage I, 56% and 89%; Stage II, 52% and 88%; Stage III, 24% and 44%; Stage IV, 22% and 34%; and overall, 30% and 49%, respectively. Eight patients (5%) died of complications.

CONCLUSIONS

Locoregional control and survival were found to be related to site, extent of disease, and fractionation schedule. Although outcomes have improved in recent years, the morbidity of treatment was significant in the current study and a substantial proportion of patients died secondary to the malignancy. Cancer 2003. © 2003 American Cancer Society.
Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors
Authors: Vogt Thomas , Hafner Christian , Bross Klaus , Bataille Frauke , Jauch Karl‐Walter , Berand Anna , Landthaler Michael , Andreesen Reinhard , Reichle Albrecht
Published: October 2003

BACKGROUND

Systemic therapy options for patients with advanced angiosarcomas are limited, and their prognosis is poor. The idea of angiostatic therapy following the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic biomodulators had not been considered previously in these patients. Therefore, in a pilot study, the efficacy of metronomically scheduled, low‐dose trofosfamide in combination with the peroxisome proliferator‐activated receptor γ agonist, pioglitazone, and the selective cyclooxygenase‐2 inhibitor, rofecoxib, was evaluated in patients with advanced vascular malignancies.

METHODS

Six patients with advanced and pretreated but progressive, malignant vascular tumors (5 angiosarcomas and 1 hemangioendothelioma) received a combination of pioglitazone (45 mg per day orally) plus rofecoxib (25 mg per day orally) and, after 14 days, trofosfamide (3 × 50 mg per day orally). The therapy was administered continuously until progression was observed. If necessary, doses were modified according to side effects.

RESULTS

Two patients responded with complete remission of disease, one patient responded with partial remission, and three patients achieved stabilization of disease (no change). The median progression‐free survival was 7.7 months (range, 2–15 months). Side effects generally were mild (World Health Organization Grade 1–2). Hospitalization was not necessary.

CONCLUSIONS

This new triple combination of low‐dose metronomic trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of patients with advanced malignant vascular tumors. Cancer 2003. © 2003 American Cancer Society.
Weekly paclitaxel, estramustine phosphate, and oral etoposide in the treatment of hormone‐refractory prostate carcinoma
Authors: Meluch Anthony A. , Greco F. Anthony , Morrissey Lisa H. , Raefsky Eric L. , Steis Ronald G. , Butts James A. , Hainsworth John D.
Published: October 2003

BACKGROUND

The objective of the current study was to evaluate the efficacy and toxicity of weekly paclitaxel, oral etoposide, and estramustine phosphate in the treatment of patients with advanced, hormone‐refractory prostate carcinoma.

METHODS

Patients with hormone‐refractory prostate carcinoma who had received no more than one previous chemotherapy regimen were eligible for this trial. Forty‐two patients were treated between February 1998 and March 2000. Toxicity was excessive in the first 3 patients treated (Grade 3–4 leukopenia, 3 patients; death due to sepsis, 1 patient); the remaining 39 patients received lower doses of etoposide and estramustine phosphate (paclitaxel 50 mg/m2 as a 1‐hour, intravenous infusion on Days 1, 8, 15; etoposide 50 mg orally twice daily on Days 1–10; and estramustine phosphate 280 mg orally 3 times daily on Days 1–10). Courses were repeated every 28 days. Patients were evaluated for objective and/or serologic response after two courses of treatment; responding patients continued treatment for six courses.

RESULTS

Fourteen of 40 evaluable patients (35%) had either an objective response or a serologic response to treatment. The median survival for the entire group was 9.5 months, with 1‐year, 2‐year, and 3‐year survival rates of 38%, 12%, and 10%, respectively. Neutropenia was the most common Grade 3–4 toxicity and occurred in 38% of patients (11% of courses). Thirteen patients (33%) had severe fatigue, and 2 patients had treatment‐related deaths due to sepsis.

CONCLUSIONS

Although the three‐drug combination had activity in patients with hormone‐refractory prostate carcinoma, the results did not appear any better than the results achieved with less toxic taxane/estramustine phosphate combinations. Further development of this three‐drug regimen is not recommended. Cancer 2003. © 2003 American Cancer Society.
Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia
Authors: Giles Francis , Estey Elihu , O'Brien Susan
Published: October 2003

Gemtuzumab ozogamicin (GO) is a chemotherapeutic agent that consists of a humanized anti‐CD33 antibody (hP67.6) linked to N‐acetyl‐γ calicheamicin 1,2‐dimethyl hydrazine dichloride, a potent enediyne antitumor antibiotic. GO was approved conditionally by the Federal Drug Administration in May 2000 as single‐agent therapy for first recurrence of acute myeloid leukemia (AML) in a subset of older patients. Data on studies in AML with GO‐based regimens have been reported rapidly in addition to new observations on the target antigen, CD33. These data indicate promising new areas of investigation with GO, including its application as maintenance therapy in patients with AML and as an induction and/or maintenance agent in patients with acute promyelocytic leukemia;, and they also have highlighted challenges in the development of GO, particularly its association with hepatic venoocclusive disease. In vitro data on the mechanism of action of GO may be particularly helpful in the design of future clinical studies. Cancer 2003. © 2003 American Cancer Society.
Characterization of the dual‐specificity phosphatase PYST2 and its transcripts
Authors: Levy‐Nissenbaum Orlev , Sagi‐Assif Orit , Witz Isaac P.
Published: October 2003

PYST2 is a member of a structurally homologous subfamily of MAP kinase phosphatases. A computer‐based analysis of the PYST2 locus revealed that it harbors two alternative open reading frames promoted by two conserved promoter regions. Using Northern blot analysis and reverse transcription–polymerase chain reaction followed by sequencing and alignment of the products, we confirmed the existence of two mRNAs that were transcribed from this genomic region. Western blot analysis indicated that these transcripts were translated. Functional bioinformatic analysis of both transcripts revealed that exon 2 exists in only one of the PYST2 transcripts, designated PYST2‐L, and has the consensus elements of the phosphatase catalytic domain (PCD). We found that the translation from the PYST2‐L transcript starts 46 codons upstream from the (already‐known) PYST2 5′ sequence. Furthermore, the existence of three PYST2‐L transcripts was indicated. These transcripts differ only in their 5′ untranslated regions (5′UTRs). Unlike PYST2‐L, the other mRNA (PYST2‐S) is devoid of any known PCD. Analysis of the predicted Pyst2‐S protein revealed the presence of the vertebrate metallothionein signature I, the mammalian defensin, and the zinc‐containing alcohol dehydrogenase motifs. These motifs might confer on this protein the ability to sense changes in the cellular environment. From these and previous results, we speculate that Pyst2‐S may function as a negative regulator of Pyst2‐L. © 2003 Wiley‐Liss, Inc.
Analysis of chromosomal imbalances in de novo CD5‐positive diffuse large‐B‐cell lymphoma detected by comparative genomic hybridization
Authors: Karnan Sivasundaram , Tagawa Hiroyuki , Suzuki Ritsuro , Suguro Miyuki , Yamaguchi Motoko , Okamoto Masataka , Morishima Yasuo , Nakamura Shigeo , Seto Masao
Published: October 2003

We recently demonstrated that the prognosis for de novo CD5‐positive (CD5+) diffuse large‐B‐cell lymphoma (DLBCL) is markedly worse than that for CD5‐negative (CD5−) DLBCL. Our findings also suggested that on the basis of its clinical features CD5+ DLBCL may constitute a unique disease category. However, the genetic basis for these two categories has not been established. Therefore, we performed comparative genomic hybridization analysis (CGH) of 26 cases of CD5+ DLBCL and 44 cases of CD5− DLBCL. Several identical changes in CD5+ and CD5− DLBCLs were found, such as gains of 3q, 9p, 12q, 13q, and 18q and losses of 1p, 6q, 17p, and 19p. However, distinct differences between the two categories were also detected. These included gains of 11q21‐q24 (P = 0.032) and 16p (P = 0.005) in CD5+ DLBCL, and loss of 16p (P = 0.028) in CD5− DLBCL. A comparison with results reported for mantle cell lymphoma, chronic lymphocytic leukemia, and Richter's syndrome demonstrated that the CGH pattern of CD5+ DLBCL was markedly different. This indicates that CD5+ DLBCL constitutes a disease category distinct from that of CD5− DLBCL and other CD5+ malignancies. © 2003 Wiley‐Liss, Inc.
t(14;19)(q32;q13): A recurrent translocation in B‐cell precursor acute lymphoblastic leukemia
Authors: Robinson Hazel M. , Taylor Kerry E. , Jalali G. Reza , Cheung Kan Luk , Harrison Christine J. , Moorman Anthony V.
Published: October 2003

The recurrent t(14;19)(q32;q13) translocation associated with chronic B‐cell lymphoproliferative disorders, such as atypical chronic lymphocytic leukemia, results in the juxtaposition of the IGH@ and BCL3 genes and subsequent overexpression of BCL3. We report six patients with B‐cell precursor acute lymphoblastic leukemia who have a cytogenetically identical translocation with different breakpoints at the molecular level. Fluorescence in situ hybridization with locus‐specific probes confirmed the involvement of the IGH@ gene but showed that the breakpoint on 19q13 lay outside the region documented in t(14;19)(q32;q13)‐positive chronic lymphocytic leukemia. This newly described translocation constitutes a distinct cytogenetic subgroup that is confined to older children and younger adults with B‐cell precursor acute lymphoblastic leukemia. © 2003 Wiley‐Liss, Inc.
Transient human cortical responses during the observation of simple finger movements: A high‐resolution EEG study
Authors: Babiloni Claudio , Del Percio Claudio , Babiloni Fabio , Carducci Filippo , Cincotti Febo , Moretti Davide V. , Rossini Paolo M.
Published: October 2003

High‐resolution event‐related potentials (ERPs) were used to model the hemispherical representation of the transient cortical responses relating to the observation of movement during execution (right or left aimless finger extension). Subjects were seated in front of the observed person and looked at both their own and the observer's hand to receive similar visual feedback during the two conditions. In a visual control condition, a diode light moved at the observed person's hand. A first potential accompanying the movement execution peaked at about +110 msec over the contralateral somatomotor areas. It was followed by a potential (P300) peaking at about +350 msec over the central midline. In contrast, the potentials accompanying the movement observation peaked later over parietal‐occipital other than somatomotor areas (N200 peak, +200 msec; P300 peak, +400 msec). Notably, the N200 was maximum in left parietal area whereas the P300 was maximum in right parietal area regardless the side of the movement. They markedly differed by the potentials following the displacement of the diode light. These results suggest a rapid time evolution (∼200–400 msec) of the cortical responses characterizing the observation of aimless movements (as opposite to grasping or handling). The execution of these movements would mainly involve somatomotor cortical responses and would be scarcely founded on the visual feedback. In contrast, the observation of the same movements carried out by others would require dynamical responses of somatomotor and parietal‐occipital areas (especially of the right hemisphere), possibly for a stringent visuospatial analysis of the motor event. Hum. Brain Mapping 20:148–157, 2003. © 2003 Wiley‐Liss, Inc.
Detection and quantification of a wide range of fMRI temporal responses using a physiologically‐motivated basis set
Authors: Harms Michael P. , Melcher Jennifer R.
Published: October 2003

The temporal dynamics of fMRI responses can span a broad range, indicating a rich underlying physiology, but also posing a significant challenge for detection. For instance, in human auditory cortex, prolonged sound stimuli (∼30 sec) can evoke responses ranging from sustained to highly phasic (i.e., characterized by prominent peaks just after sound onset and offset). In the present study, we developed a method capable of detecting a wide variety of responses, while simultaneously extracting information about individual response components, which may have different neurophysiological underpinnings. Specifically, we implemented the general linear model using a novel set of basis functions chosen to reflect temporal features of cortical fMRI responses. This physiologically‐motivated basis set (the “OSORU” basis set) was tested against (1) the commonly employed “sustained‐only” basis “set” (i.e., a single smoothed “boxcar” function), and (2) a sinusoidal basis set, which is capable of detecting a broad range of responses, but lacks a direct relationship to individual response components. On data that included many different temporal responses, the OSORU basis set performed far better overall than the sustained‐only set, and as well or better than the sinusoidal basis set. The OSORU basis set also proved effective in exploring brain physiology. As an example, we demonstrate that the OSORU basis functions can be used to spatially map the relative amount of transient vs. sustained activity within auditory cortex. The OSORU basis set provides a powerful means for response detection and quantification that should be broadly applicable to any brain system and to both human and non‐human species. Hum. Brain Mapp. 20:168–183, 2003. © 2003 Wiley‐Liss, Inc.
How much confidence should we place in efficiency estimates?
Authors: Street Andrew
Published: October 2003

Ordinary least squares (OLS) and stochastic frontier (SF) analyses are commonly used to estimate industry‐level and firm‐specific efficiency. Using cross‐sectional data for English public hospitals, a total cost function based on a specification developed by the English Department of Health is estimated. Confidence intervals are calculated around the OLS residuals and around the inefficiency component of the SF residuals. Sensitivity analysis is conducted to assess whether conclusions about relative performance are robust to choices of error distribution, functional form and model specification. It is concluded that estimates of relative hospital efficiency are sensitive to estimation decisions and that little confidence can be placed in the point estimates for individual hospitals. The use of these techniques to set annual performance targets should be avoided. Copyright © 2002 John Wiley & Sons, Ltd.
Estimating mean hospital cost as a function of length of stay and patient characteristics
Authors: Polverejan Elena , Gardiner Joseph C. , Bradley Cathy J. , Holmes‐Rovner Margaret , Rovner David
Published: October 2003

Statistical models have been used to assess the influence of clinical and demographic factors on hospital charge and length of stay (LOS). Hospital costs constitute a significant proportion of overall expenditure in health care. With escalating costs, knowing the correlates of LOS and in‐hospital cost is important for decisions on allocating resources.

However, hospital charge and LOS are correlated. We describe two regression models that permit estimation of mean charges as a function of patient hospital stay and adjust for the influence of patient characteristics and treatment procedures on LOS and charge. In the first model, the mean charge over a specified duration is a weighted average of the expected cumulative charge, with weighting determined by the distribution of LOS. The second model for LOS and charge explicitly accounts for their correlation and yields estimates of the average charge per average LOS.

The methods are applied to assess mean charges and mean charge per day by cardiac procedure in a cohort of patients hospitalized for acute myocardial infarction, while adjusting for the impact of patient demographic and clinical factors on LOS and charge.

For relatively short hospital stays, and when only total hospital charges are available, these models provide a flexible approach to estimating summary measures on resource use while controlling for the effects of covariates on LOS and charge. Copyright © 2002 John Wiley & Sons, Ltd.
Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery
Authors: Wong Ling Yuen , Wei William Ignace , Lam Lai Kun , Yuen Anthony Po Wing
Published: October 2003

Purpose.

The efficacy of salvage treatment of recurrent head and neck squamous cell carcinomas (HNSCC) after primary curative surgery was evaluated.

Methods.

The management outcome of 377 patients who had recurrent squamous cell carcinoma of oral cavity, oropharynx, hypopharynx, and larynx after primary curative surgery was reviewed.

Results.

The surgical salvage rates of recurrence were 29% local, 30% tracheostomal, 56% unilateral nodal recurrence of previously undissected neck, 32% of unilateral neck recurrence after prior neck dissection, and 11% lung metastasis. The 5‐year tumor‐free actuarial survival rates of those patients who received surgical salvage was 35% for local recurrence, 32% for unilateral nodal recurrence of the previously undissected neck, and 18% for nodal recurrence of the previously dissected neck. One patient of six with tracheostomal recurrence salvaged with surgery and one patient of six with lung metastasis salvaged with lobectomy survived without tumor at 5 years. There was no 5‐year survivor of all patients salvaged with other nonsurgical methods. The mean survival of patients without surgical salvage was 6 months.

Conclusions.

There was a moderate chance of cure after surgical salvage of locoregional recurrent HNSCC. Surgical salvage was, however, only feasible for early recurrent tumor. Close follow‐up surveillance of early recurrence is essential after primary treatment of patients. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Current management of benign parotid tumors—The role of limited superficial parotidectomy
Authors: O'Brien Christopher J.
Published: October 2003

Background.

Parotid tumors are mostly benign, but their evaluation and treatment require a thorough knowledge of the relevant anatomy and pathology. Surgical treatment of benign tumors is aimed at complete removal of the mass with facial nerve preservation. The aim of this study was to evaluate the results of treatment of benign parotid neoplasms when surgery entailed limited superficial parotidectomy.

Methods.

All patients with benign parotid tumors treated by the author from 1988 to 2002 were reviewed. Data had been prospectively accessioned onto the computerized database of the Department of Head and Neck Surgery, RPAH. Limited superficial parotidectomy was carried out in all previously untreated patients with tumors superficial to the plane of the facial nerve. Median follow‐up time was 6 years (range, 1–14 years).

Results.

A total of 363 parotidectomies was carried out on 355 patients, 29 of whom (8%) were previously treated. Tumors arose deep to the plane of the facial nerve in 40 patients (11%), and, of these, 16 occupied the parapharyngeal space. Pleomorphic adenoma (70%) and Warthin's tumors (15%) were the most common pathologic types. Temporary postoperative facial weakness occurred after 98 operations (27%). Facial weakness was permanent in 2.5% of patients (9 cases) who had normal preoperative function; however, in this group the facial nerve was intentionally resected in 2 patients, 3 others had had previous surgery, and 1 had a deep lobe tumor. Tumor recurrence developed in three patients (0.8%), two of whom had been previously treated.

Conclusion.

Complete superficial parotidectomy is unnecessary in the treatment of benign localized parotid tumors. Limited parotidectomy is associated with very low rates of morbidity and recurrence. Preoperative investigations should be used selectively; however, the author recommends routine (or at least liberal) use of fine‐needle aspiration biopsy. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Tumor thickness influences prognosis of T1 and T2 oral cavity cancer—but what thickness?
Authors: O'Brien Christopher J. , Lauer Christopher S. , Fredricks Susanne , Clifford Anthony R. , McNeil Edward B. , Bagia Jai S. , Koulmandas Christina
Published: October 2003

Background.

Previous studies have demonstrated that tumor thickness might influence prognosis in oral cancer, but the significant point at which outcome changes has varied from 1.5 mm to 6 mm. The clinical relevance of thickness remains unclear, and a reproducible prognostic “breakpoint” needs to be defined.

Methods.

Tumor thickness was measured in 145 oral cavity squamous cancers, clinically staged T1 (n = 62) or T2 (n = 83). Clinical and pathologic data were collected prospectively between 1988 and 2000, but thickness was measured on paraffin sections for this study. Minimum follow‐up was 2 years, and thickness was correlated with local control, cervical node involvement, and survival. Patients with clinically positive nodes (n = 21) were not excluded. Overall, 55 patients had pathologic node involvement at some time in their disease.

Results.

Median tumor thickness was 6.2 mm, and there was little variation between sites: tongue, 6.4 mm; floor of mouth, 6.6 mm; and other sites, 5.7 mm. Median thickness for T1 tumors was 4.3 mm, significantly less than the T2 group, 8 mm (p < .01). Median thickness also varied significantly for tumors with associated nodal disease (8.5 mm) and without nodal disease (5.8 mm) (p < .01). Prognosis changed significantly at a cutoff of 4 mm with local control, nodal disease, and survival rates of 91%, 8%, and 100%, respectively, for tumors <4 mm compared with 84%, 48%, and 74% for those 4 mm or more thick (p < .01). Subgrouping greater than and less than 3 mm and 5 mm also showed a difference but with poorer discrimination. Thickness and pathologic nodal involvement were highly significant independent prognostic factors.

Conclusions.

Tumor thickness is a highly significant, objectively measurable prognostic factor in early stage oral cancers. There is a need to standardize techniques of measurement to allow a multiinstitutional study to be carried out. This will facilitate the development of strategies aimed at improving the outcome of higher risk patients. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Localisation of WE‐14 immunoreactivity in the developing mouse limbo‐corneal nerve net
Authors: Curry William James , Brockbank Simon , Mccollum Anna Patricia , Boyle Cliona , Gibson David
Published: October 2003

WE‐14 is generated in subpopulations of chromogranin A immunopositive endocrine cells and neurons including those innervating the anterior uvea. This study investigated WE‐14 in intact sclero‐limbo‐corneal tissue from embryonic (E17), neonatal (N0‐N16), and adult mice using immunocytochemistry and confocal scanning laser microscopy. Weak WE‐14 immunostaining was observed at birth in nerve fibre tracts entering the corneal mid‐stroma from the limbo‐scleral junction. Immunopositive fibre tracts were evident throughout the cornea at N3; by N5 the mid‐stromal plexus had begun to generate fibre populations extending toward the developing corneal epithelium, and some varicose fibres terminated amongst the developing epithelium. Immunostaining was evident at N7 in the developing limbo‐scleral nerve net and some fibres exhibited a close association with unidentified vascular elements. By N11 and in subsequent neonates, the cornea had developed a distinct stratified nerve net composed of thick mid‐stromal and thinner upper stromal nerve fibre bundles; both possessed populations of varicose WE‐14 immunopositive fibres. In the adult, a sub‐epithelial network of varicose WE‐14 immunopositive fibres were evident at the limbo‐scleral junction. Some fibres exhibited a close association with unidentified vascular elements, while others extended into the upper peripheral corneal stroma. WE‐14 was evident in leashes throughout the basal corneal epithelium and generated fibres ramifying between the stratified epithelium with some fibres terminating amongst the outermost corneal epithelia. This study has demonstrated that WE‐14 was evident in the limbo‐corneal nerve net at birth and that its detection parallels corneal development to adulthood, where WE‐14 is evident in a subpopulation of nerve fibres. Microsc. Res. Tech. 62:408–414, 2003. © 2003 Wiley‐Liss, Inc.
Temporal and topographic ultrastructural alterations of rat heart myofibrils caused by thyroid hormone
Authors: Ferreira Paula Juliana , L'Abbate Carolina , Abrahamsohn Paulo Alexandre , Gouveia Cecilia Azevedo , Moriscot Anselmo Sigari
Published: October 2003

In order to further our understanding regarding the temporal and topographic ultrastructural aspects of the myocardium under thyrotoxicosis, thyroxine (T4; 25 and 100 μg/100 g bw) was administered to young rats 24 hours after birth until 15 days. The animals were then sacrificed, the hearts excised and weighed, and the ventricle tissue samples were then processed for confocal and transmission electron microscopy. At 48/72 hours and 1 week after initiation of T4 treatment with 100 μg/100 g bw, numerous lamellar bodies (probably formed by phospholipids) progressively accumulated in the heart. These bodies were observed in the cytosol, inside mitochondria and in the extracellular matrix. At 2 weeks of T4 treatment with 100 μg/100 g bw, lamellar bodies were virtually absent. Changes in cell shape, disorganization of intercellular junctions, and substantial myofibrillar disarray were observed in many cardiomyocytes. A gradient of myofibrillar disarray, which increased in abundance and intensity from the endocardium to the epicardium, was also observed. Immunocytochemical staining for desmin showed that the arrangement of this protein was disorganized in many cells of T4‐treated rats as compared with normal ones, confirming ultrastructural data. The predominant appearance of myofibrillar disarray, associated with disorganization of cytoskeletal proteins in the deep myocardium, may be due to higher mechanical wall stress and consequent higher metabolic demand. Alternatively, differential sensitivity of cardiomyocytes to thyroid hormone in different areas is also a possibility. Microsc. Res. Tech. 62:451–459, 2003. © 2003 Wiley‐Liss, Inc.
Historical origins of schizophrenia: Two early madmen and their illness
Authors: Heinrichs R. Walter
Published: October 2003

Schizophrenia is a serious mental illness with a remarkably short recorded history. Unlike depression and
mania, which are recognizable in ancient texts, schizophrenia‐like disorder appeared rather suddenly in
the psychiatric literature of the early nineteenth century. This could mean that the illness is a recent disease
that was largely unknown in earlier times. But perhaps schizophrenia existed, embedded and disguised within more
general concepts of madness and within the arcane languages and cultures of remote times. Both possibilities
present major challenges to historical and psychiatric scholarship. These challenges are explored in this paper
by presenting two “new” cases of schizophrenia, one from the eighteenth and one from the fourteenth
century. The cases suggest that the illness may have existed as early as the medieval period. However,
establishing the population prevalence of schizophrenia in earlier times—and therefore resolving the
permanence‐recency debate—may not be a feasible enterprise. © 2003 Wiley Periodicals, Inc.
Thermodynamic characteristics and numerical modeling of internal nitridation of nickel base alloys
Authors: Christ H.‐J. , Chang S.‐Y. , Krupp U.
Published: October 2003

Kinetics and thermodynamics of the process of internal nitridation of various nickel‐base alloys have been investigated in oxygen‐free nitrogen atmospheres. Furthermore, the influence of formation and spalling of a protective oxide scale on the internal nitridation behavior of the alloys was studied by isothermal and cyclic oxidation tests in air. In general, nitridation kinetics of model nickel‐base alloys of the system Ni‐Cr‐Ti was found to obey a parabolic rate law indicating that the nitridation process is diffusion‐controlled. The temperature dependence of the nitridation rate constants is well described by an equation of the Arrhenius type. A thermodynamic calculation of the Ni‐Cr‐Ti‐Al‐N system was used to determine the nitrogen solubility in respective alloys as a function of temperature and alloy composition. The results show that a higher chromium content gives rise to an increase in the nitrogen solubility of Ni‐Cr‐Ti alloys leading to an increased nitridation rate in accordance with the experimental observations. From the calculated values for the nitrogen solubility, the diffusion coefficients of nitrogen were assessed using Wagner's classical theory of internal oxidation. A computer model of internal nitridation was developed that combines a commercial thermodynamic software (ChemApp) with a finite‐difference diffusion calculation. It was found that this model describes the internal nitridation process in reasonable agreement with the experimental results and allows to treat the case of simultaneous formation of different nitrides. The dependence of internal nitridation behavior on spalling and cracking of the oxide was incorporated into the simulation on the basis of simple assumptions showing that this calculation method successfully applies also to complex internal corrosion processes.
Nitridation in NH3‐H2O‐mixtures
Authors: Grabke H. J. , Strauss S. , Vogel D.
Published: October 2003

Exposures were conducted of iron, nickel, ferritic 1‐18%Cr steels, austenitic 18%Cr‐9%Ni‐ and 20%Cr‐31%Ni‐steels and a 16%Cr‐Ni‐base alloy at 500°C in He‐30%H2O and 70%H2O‐30%NH3, to compare the corrosion behaviour of these materials in water vapor as in conventional power plants with their behaviour in a NH3‐H2O mixture, i.e. under conditions of the “Kalina‐cycle”. After 50 h in He‐H2O generally a dense oxide scale had grown on iron and on the steels, whereas the scale grown in NH3‐H2O was porous, due to initial formation of the γ′‐ and ε‐nitrides, which are converted to Fe3O4 later. The porous scale allows internal nitridation of the Cr‐steels, nitrogen is transferred into the metal phase and reacts to finely dispersed CrN‐precipitates. This process causes stresses in the material and formation of cracks. The higher the Cr‐content of the material, the worse is the damage of the materials surface.

Least corrosion damage occurs for iron and the 1%CrMo‐steel, however, the inward penetration of nitridation is greatest, and after 5 years on the low Cr‐steel a layer of about 15 mm would be embrittled by internal nitridation, formation of γ′ and ε‐nitride layers and external oxidation.

Nickel is strongly damaged by intermediate formation of instable Ni3N, which causes internal stresses and cracking, but also pore formation by its decomposition. The surface region of the 15%Cr‐Ni‐base alloy is also destroyed by internal nitridation and extrusion of Ni‐particles, while for this material the inward penetration of nitridation is relatively slow due to the low solubility and diffusivity of N in Ni and Ni‐alloys.