bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal cancer screening awareness among physicians in Greece
Authors: Xilomenos Apostolos , Mauri Davide , Kamposioras Konstantinos , Gkinosati Athanasia , Zacharias Georgios , Sidiropoulou Varvara , Papadopoulos Panagiotis , Chatzimichalis Georgios , Golfinopoulos Vassilis , Peponi Christina ,   Panhellenic Association for Continual Medical Research (PACMeR)
Published: June 2006

Background

Data comparison between SEER and EUROCARE database provided evidence that colorectal cancer survival in USA is higher than in European countries. Since adjustment for stage at diagnosis markedly reduces the survival differences, a screening bias was hypothesized. Considering the important role of primary care in screening activities, the purpose of the study was to investigate the colorectal cancer screening awareness among Hellenic physicians.

Methods

211 primary care physicians were surveyed by mean of a self-reported prescription-habits questionnaire. Both physicians' colorectal cancer screening behaviors and colorectal cancer screening recommendations during usual check-up visits were analyzed.

Results

Only 50% of physicians were found to recommend screening for colorectal cancer during usual check-up visits, and only 25% prescribed cost-effective procedures. The percentage of physicians recommending stool occult blood test and sigmoidoscopy was 24% and 4% respectively. Only 48% and 23% of physicians recognized a cancer screening value for stool occult blood test and sigmoidoscopy. Colorectal screening recommendations were statistically lower among physicians aged 30 or less (p = 0.012). No differences were found when gender, level and type of specialization were analyzed, even though specialists in general practice showed a trend for better prescription (p = 0.054).

Conclusion

Contemporary recommendations for colorectal cancer screening are not followed by implementation in primary care setting. Education on presymptomatic control and screening practice monitoring are required if primary care is to make a major impact on colorectal cancer mortality.
Health seeking behaviour, health system experience and tuberculosis case finding in Gambians with cough
Authors: Kasse Yaya , Jasseh Momodou , Corrah Tumani , Donkor Simon A , Antonnio Martin , Jallow Adama , Adegbola Richard A , Hill Philip C
Published: June 2006

Background

Studies in Africa investigating health-seeking behaviour by interviewing tuberculosis patients have revealed patient knowledge issues and significant delays to diagnosis. We aimed to study health-seeking behaviour and experience of those with cough in The Gambia and to identify whether they had tuberculosis.

Methods

During a round of a population under 3-monthly demographic surveillance, we identified people >10 years old who had been coughing ≥ 3 weeks. A questionnaire was administered concerning demographic data, cough, knowledge, health seeking, and experience at health facilities. Case finding utilised sputum smear and chest X-ray.

Results

122/29,871 coughing individuals were identified. Of 115 interviewed, 93 (81%) had sought treatment; 76 (81.7%) from the health system. Those that visited an alternative health provider first were significantly older than those who visited the health system first (p = 0.03). The median time to seek treatment was 2 weeks (range 0 – 106). 54 (58.1%) made their choice of provider because they believed it was right. Of those who left the health system to an alternative provider (n = 13): 7 believed it was the best place, 3 cited cost and 2 failure to improve. 3 cases were identified by sputum analysis, 11 more by X-ray; all had visited the health system first. Total 'excess' cough time was 1079 person weeks.

Conclusion

The majority of people with cough in this population seek appropriate help early. Improved case detection might be achieved through the use of chest X-ray in addition to sputum smear.
Why do adult women in Vietnam take iron tablets?
Authors: Aikawa Ritsuko , Jimba Masamine , Nguen Khan C , Zhao Yun , Binns Colin W , Lee Mi Kyung
Published: June 2006

Background

Conducting iron supplementation programs has been a major strategy to reduce iron deficiency anemia in pregnancy. However, only a few countries have reported improvements in the anemia rate at a national level. The strategies used for control of nutrition problems need regular review to maintain and improve their effectiveness. The objective of this study was to analyze the factors in compliance with taking iron tablets, where daily doses of iron (60 mg) and folic acid (400 μg) were distributed in rural Vietnamese communes.

Methods

A cross sectional survey was conducted in Nghe An province, Vietnam in January, 2003. The study population was adult women aged less than 35 years who delivered babies between August 1st 2001 and December 1st 2002 (n = 205), of which 159 took part in the study. Data for the study were collected from a series of workshops with community leaders, focus group discussions with community members and a questionnaire survey.

Results

Improvements in the rate of anemia was not given a high priority as one of the commune's needs, but the participants still made efforts to continue taking iron tablets. Two major factors motivated the participants to continue taking iron tablets; their experience of fewer spells of dizziness (50%), and their concern for the health of their newborn baby (54%). When examining the reasons for taking iron tablets for at least 5–9 months, the most important factor was identified as 'a frequent supply of iron tablets' (OR = 11.93, 95% CI: 4.33–32.85).

Conclusion

The study found that multiple poor environmental risk factors discouraged women from taking iron tablets continuously. The availability (frequent supply) of iron tablets was the most effective way to help adult women to continue taking iron tablets.
Optimal search strategies for detecting cost and economic studies in EMBASE
Authors: McKinlay R James , Wilczynski Nancy L , Haynes R Brian ,   the Hedges Team
Published: June 2006

Background

Economic evaluations in the medical literature compare competing diagnosis or treatment methods for their use of resources and their expected outcomes. The best evidence currently available from research regarding both cost and economic comparisons will continue to expand as this type of information becomes more important in today's clinical practice. Researchers and clinicians need quick, reliable ways to access this information. A key source of this type of information is large bibliographic databases such as EMBASE. The objective of this study was to develop search strategies that optimize the retrieval of health costs and economics studies from EMBASE.

Methods

We conducted an analytic survey, comparing hand searches of journals with retrievals from EMBASE for candidate search terms and combinations. 6 research assistants read all issues of 55 journals indexed by EMBASE for the publishing year 2000. We rated all articles using purpose and quality indicators and categorized them into clinically relevant original studies, review articles, general papers, or case reports. The original and review articles were then categorized for purpose (i.e., cost and economics and other clinical topics) and depending on the purpose as 'pass' or 'fail' for methodologic rigor. Candidate search strategies were developed for economic and cost studies, then run in the 55 EMBASE journals, the retrievals being compared with the hand search data. The sensitivity, specificity, precision, and accuracy of the search strategies were calculated.

Results

Combinations of search terms for detecting both cost and economic studies attained levels of 100% sensitivity with specificity levels of 92.9% and 92.3% respectively. When maximizing for both sensitivity and specificity, the combination of terms for detecting cost studies (sensitivity) increased 2.2% over the single term but at a slight decrease in specificity of 0.9%. The maximized combination of terms for economic studies saw no change in sensitivity from the single term and only a 0.1% increase in specificity.

Conclusion

Selected terms have excellent performance in the retrieval of studies of health costs and economics from EMBASE.
Quality of life in patients with psoriasis
Authors: Bhosle Monali J , Kulkarni Amit , Feldman Steven R , Balkrishnan Rajesh
Published: June 2006

Psoriasis is one of the prevalent skin conditions in the United States. This chronic condition has a significant negative impact on patients' quality of life. Psoriasis has been linked to the depression and suicidal tendencies in the patients. The costs associated with decrements in quality of life, lost productivity, and work absenteeism may be enormous, increasing overall costs associated with the disease management. This review attempts to outline different quality of life measures available for psoriasis and describes their use in studies examining patient reported outcomes associated with pharmacological interventions for psoriasis. Factors associated with quality of life in psoriasis patients are described. It further describes physician's role in the psoriasis management to improve patients' overall well-being.
Xanthogranulomatous prostatitis: a mimic of carcinoma of prostate
Authors: Rafique Muhammad , Yaqoob Nausheen
Published: June 2006

Background

Xanthogranulomatous prostatitis is an unusual benign inflammatory process of prostate. Clinically it mimics prostatic carcinoma, requiring pathological examination for diagnosis.

Case presentation

A 60-year-old patient presented with 6 months history of increasing difficulty in micturition. On digital rectal examination prostate was hard and nodular and estimated weight was 50-gram. His serum prostate specific antigen (PSA) was 150 ng/ml. Clinically a locally advanced carcinoma of prostate was suspected. In view of severe obstructive urinary symptoms and significant post-micturition residual urine, transurethral resection of prostate was carried out. Histopathological examination of resected prostatic tissue revealed xanthogranulomatous prostatitis with no evidence of malignancy. Patient remains symptom free at 16 months follow-up and serum PSA has decreased to 6 ng/ml.

Conclusion

Xanthogranulomatous prostatitis is a benign inflammatory disorder of prostate that can clinically and even biochemically mimic prostatic carcinoma. A high degree of suspecion and close co-operation with pathologist is necessary for the diagnosis of xanthogranulomatous prostatitis.
Three rounds (1R/2R/3R) of genome duplications and the evolution of the glycolytic pathway in vertebrates
Authors: Steinke Dirk , Hoegg Simone , Brinkmann Henner , Meyer Axel
Published: June 2006

Background

Evolution of the deuterostome lineage was accompanied by an increase in systematic complexity especially with regard to highly specialized tissues and organs. Based on the observation of an increased number of paralogous genes in vertebrates compared with invertebrates, two entire genome duplications (2R) were proposed during the early evolution of vertebrates. Most glycolytic enzymes occur as several copies in vertebrate genomes, which are specifically expressed in certain tissues. Therefore, the glycolytic pathway is particularly suitable for testing theories of the involvement of gene/genome duplications in enzyme evolution.

Results

We assembled datasets from genomic databases of at least nine vertebrate species and at least three outgroups (one deuterostome and two protostomes), and used maximum likelihood and Bayesian methods to construct phylogenies of the 10 enzymes of the glycolytic pathway. Through this approach, we intended to gain insights into the vertebrate specific evolution of enzymes of the glycolytic pathway. Many of the obtained gene trees generally reflect the history of two rounds of duplication during vertebrate evolution, and were in agreement with the hypothesis of an additional duplication event within the lineage of teleost fish. The retention of paralogs differed greatly between genes, and no direct link to the multimeric structure of the active enzyme was found.

Conclusion

The glycolytic pathway has subsequently evolved by gene duplication and divergence of each constituent enzyme with taxon-specific individual gene losses or lineage-specific duplications. The tissue-specific expression might have led to an increased retention for some genes since paralogs can subdivide the ancestral expression domain or find new functions, which are not necessarily related to the original function.
Boosting with intranasal dendrimeric Aβ1–15 but not Aβ1–15 peptide leads to an effective immune response following a single injection of Aβ1–40/42 in APP-tg mice
Authors: Seabrook Timothy J , Jiang Liying , Thomas Katelyn , Lemere Cynthia A
Published: June 2006

Background

Immunotherapy for Alzheimer's disease (AD) is emerging as a potential treatment. However, a clinical trial (AN1792) was halted after adverse effects occurred in a small subset of subjects, which may have been caused by a T cell-mediated immunological response. In general, aging limits the humoral immune response, therefore, immunogens and vaccination regimes are required that induce a strong antibody response with less potential for an adverse immune response.

Method

In the current study, we immunized both wildtype and J20 APP-tg mice with a priming injection of Aβ1–40/42, followed by multiple intranasal boosts with the novel immunogen dAβ1–15 (16 copies of Aβ1–15 on a lysine tree), Aβ1–15 peptide or Aβ1–40/42 full length peptide.

Results

J20 APP-tg mice primed with Aβ1–40/42 subcutaneously and subsequently boosted intranasally with Aβ1–15 peptide did not generate a cellular or humoral immune response. In contrast, J20 APP-tg mice boosted intranasally with dAβ1–15 or full length Aβ1–40/42 produced high levels of anti-Aβ antibodies. Splenocyte proliferation was minimal in mice immunized with dAβ1–15. Wildtype littermates of the J20 APP-tg mice produced higher amounts of anti-Aβ antibodies compared to APP-tg mice but also had low T cell proliferation. The anti-Aβ antibodies were mainly composed of IgG2b and directed to an epitope within the Aβ1–7 region, regardless of the immunogen. Examination of the brain showed a significant reduction in Aβ plaque burden in the J20 APP-tg mice producing antibodies compared to controls. Biochemically, Aβ40 or Aβ42 were also reduced in brain homogenates and elevated in plasma but the changes did not reach significance.

Conclusion

Our results demonstrate that priming with full length Aβ40/42 followed by boosting with dAβ1–15 but not Aβ1–15 peptide led to a robust humoral immune response with a minimal T cell response in J20 APP-tg mice. In addition, Aβ plaque burden was reduced in mice producing anti-Aβ antibodies. Interestingly, wildtype mice produced higher levels of anti-Aβ antibodies, indicating that immune tolerance may be present in J20 APP-tg mice. Together, these data suggest that dAβ1–15 but not Aβ1–15 peptide may be useful as a boosting immunogen in an AD vaccination regime.
Inhibitory Role of Supraspinal P2X3/P2X2/3Subtypes on Nociception in Rats
Authors: Fukui Masato , Nakagawa Takayuki , Minami Masabumi , Satoh Masamichi , Kaneko Shuji
Published: June 2006

Extracellular ATP is known to mediate synaptic transmission as a neurotransmitter or a neuromodulator via ionotropic P2X and metabotropic P2Y receptors. Several lines of evidence have suggested that ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors, in which the P2X3subtype is considered as an important candidate for the effect. Conversely, we previously found that the activation of supraspinal P2X receptors evoked antinociception. However, the subtypes responsible for the antinociception via supraspinal P2X receptors remain unclear. In the present study, we showed that intracerebroventricular (i.c.v.) pretreatment with A-317491 (1 nmol), the novel non-nucleotide antagonist selective for P2X3and P2X2/3receptors, attenuated the antinociceptive effect produced by i.c.v. administered α,β-methylene-ATP (10 nmol), the P2X receptor agonist, in rats. Similarly, the abolishment of the P2X3receptor mRNA in the brainstem by repeated i.c.v. pretreatments with antisense oligodeoxynucleotide for P2X3gene once a day for 5 consecutive days diminished the antinociceptive effect of α,β-methylene-ATP. Furthermore, i.c.v. administration of A-317491 (1 and 10 nmol) significantly enhanced the inflammatory nociceptive behaviors induced by the intraplantar injection of formalin and intraperitoneal injection of acetic acid. Taken together, these results suggest that supraspinal P2X3/P2X2/3receptors play an inhibitory role in pain transmission.
The Dapsone Hypersensitivity Syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations
Authors: Kosseifi Semaan G , Guha Bhuvana , Nassour Dima N , Chi David S , Krishnaswamy Guha
Published: June 2006

4,4'-Diaminodiphenylsulphone (Dapsone) is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS), the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems) involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.
Effects of cyanobacterial extracellular products and gibberellic acid on salinity tolerance in Oryza sativaL
Authors: Rodríguez AA , Stella AM , Storni MM , Zulpa G , Zaccaro MC
Published: June 2006

Salt stress is one of the most serious factors limiting the productivity of rice, the staple diet in many countries. Gibberellic acid has been reported to reduce NaCl-induced growth inhibition in some plants including rice. Most paddy soils have a natural population of Cyanobacteria, prokaryotic photosynthethic microorganisms, which synthesize and liberate plant growth regulators such as gibberellins that could exert a natural beneficial effect on salt stressed rice plants. The aim of this work was to evaluate the effect of the cyanobacterium Scytonema hofmanni extracellular products on the growth of rice seedlings inhibited by NaCl and to compare it with the effect of the gibberellic acid in the same stress condition. Growth (length and weight of the seedlings) and biochemical parameters (5-aminolevulinate dehydratase activity, total free porphyrin and pigments content) were evaluated.

Salt exposure negatively affected all parameters measured, with the exception of chlorophyll. Chlrorophyll concentrations nearly doubled upon exposure to high salt. Gibberellic acid counteracted the effect of salt on the length and dry weight of the shoot, and on carotenoid and chlorophyll b contents. Extracellular products nullified the salt effect on shoot dry weight and carotenoid content; partially counteracted the effect on shoot length (from 54% to 38% decrease), root dry weight (from 59% to 41% decrease) and total free porphyrin (from 31 to 13% decrease); reduced by 35% the salt increase of chlorophyll a; had no effect on root length and chlorophyll b. Gibberellic acid and extracellular products increased 5-aminolevulinate dehydratase activity over the control without salt. When coincident with high salinity, exposure to either EP or GA3, resulted in a reversal of shoot-related responses to salt stress. We propose that Scytonema hofmanni extracellular products may counteract altered hormone homeostasis of rice seedlings under salt stress by producing gibberellin-like plant growth regulators.
The status of research on glaciers and global glacier recession: a review
Authors: Barry Roger G.
Published: June 2006

Mountain glaciers are key indicators of climate change, although the climatic variables involved differ regionally and temporally. Nevertheless, there has been substantial glacier retreat since the Little Ice Age and this has accelerated over the last two to three decades. Documenting these changes is hampered by the paucity of observational data. This review outlines the measurements that are available, new techniques that incorporate remotely sensed data, and major findings around the world. The focus is on changes in glacier area, rather than estimates of mass balance and volume changes that address the role of glacier melt in global sea-level rise. The glacier observations needed for global climate monitoring are also outlined.
Quaternary glacial history of the Mediterranean mountains
Authors: Hughes P. D. , Woodward J. C. , Gibbard P. L.
Published: June 2006

Glacial and periglacial landforms are widespread in the mountains of the Mediterranean region. The evidence for glacial and periglacial activity has been studied for over 120 years and it is possible to identify three phases of development in this area of research. First, a pioneer phase characterized by initial descriptive observations of glacial landforms; second, a mapping phase whereby the detailed distribution of glacial landforms and sediments have been depicted on geomorphological maps; and, third, an advanced phase characterized by detailed understanding of the geochronology of glacial sequences using radiometric dating alongside detailed sedimentological and stratigraphical analyses. It is only relatively recently that studies of glaciated mountain terrains in the Mediterranean region have reached an advanced phase and it is now clear from radiometric dating programmes that the Mediterranean mountains have been glaciated during multiple glacial cycles. The most extensive phases of glaciation appear to have occurred during the Middle Pleistocene. This represents a major shift from earlier work whereby many glacial sequences were assumed to have formed during the last cold stage. Glacial and periglacial deposits from multiple Quaternary cold stages constitute a valuable palaeoclimatic record. This is especially so in the Mediterranean mountains, since mountain glaciers in this latitudinal zone would have been particularly sensitive to changes in the global climate system.
Disturbance regime landscapes: mountain drainage systems interrupted by large rockslides
Authors: Hewitt Kenneth
Published: June 2006

The paper examines the role of rockslide-rock avalanches in mountain landscapes, and the landforms associated with them. While the landslides are extremely short-lived events, rock wall detachment scars and rock avalanche deposits can persist for long periods as influences on landscape development. Especially significant are rock avalanches with complex runout and emplacement related to interactions with rugged terrain or deformable substrates. Their characteristics greatly increase the scope of landscape disturbance. Hundreds of rock avalanches are now known, worldwide, that have formed crossvalley barriers interrupting mountain drainage systems. Many have done so for millennia or tens of millennia. They give rise to distinctive sediment assemblages, constructional and erosion landforms generated by other processes responding to the landslides and constrained by them. A landslide interruption epicycle of five phases is described, and related sediment assemblages. These provide the basis for defining a landslide interrupted valley landsystem. Its full significance is seen in mountain drainage basins affected by multiple landslide interruptions. These create naturally fragmented fluvial systems, in which a disturbance regime geomorphology is identified. Stream profiles, sediment delivery, and related landforms are kept in a chronic state of disequilibrium with respect to climatic and geotectonic controls, and drainage organization. The transHimalayan Upper Indus Basin provides an example, a large high mountain drainage system fragmented by more than 170 late Quaternary rock avalanches. In this case, as elsewhere, misidentification of rock avalanches led to neglect of their role in Quaternary histories. The nature and limitations of disturbance regime geomorphology are discussed, and broader implications for mountain landscapes.
Phase II Trial of Idiotype Vaccination in Previously Treated Patients With Indolent Non-Hodgkin’s Lymphoma Resulting in Durable Clinical Responses
Authors: Redfern Charles H. , Guthrie Troy H. , Bessudo Alberto , Densmore John J. , Holman Peter R. , Janakiraman Nalini , Leonard John P. , Levy Richard L. , Just Richard G. , Smith Mitchell R. , Rosenfelt Fred P. , Wiernik Peter H. , Carter William D. , Gold Daniel P. , Melink Teresa J. , Gutheil John C. , Bender John F.
Published: June 2006

Purpose

To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin’s lymphoma.

Patients and Methods

Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 μg on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated.

Results

Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id.

Conclusion

This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.
Frequency, Characteristics, and Reversibility of Peripheral Neuropathy During Treatment of Advanced Multiple Myeloma With Bortezomib
Authors: Richardson Paul G. , Briemberg Hannah , Jagannath Sundar , Wen Patrick Y. , Barlogie Bart , Berenson James , Singhal Seema , Siegel David S. , Irwin David , Schuster Michael , Srkalovic Gordan , Alexanian Raymond , Rajkumar S. Vincent , Limentani Steven , Alsina Melissa , Orlowski Robert Z. , Najarian Kevin , Esseltine Dixie , Anderson Kenneth C. , Amato Anthony A.
Published: June 2006

Purpose

To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma.

Patients and Methods

Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m2 intravenous bolus on days 1, 4, 8, and 11, every 21 days, for up to eight cycles. Peripheral neuropathy was evaluated at baseline, during the study, and after the study by patient-reported symptoms using the Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire and neurologic examination. During the study, peripheral neuropathy was also evaluated by investigator assessment. A subset of patients underwent nerve conduction studies (n = 13).

Results

Before treatment, 194 (81%) of 239 patients had peripheral neuropathy by FACT/GOG-Ntx questionnaire, and 203 (83%) of 244 patients had peripheral neuropathy by neurologic examination. Treatment-emergent neuropathy was reported in 35% of patients, including 37% (84 of 228 patients) receiving bortezomib 1.3 mg/m2 and 21% (six of 28 patients) receiving bortezomib 1.0 mg/m2. Grade 1 or 2, 3, and 4 neuropathy occurred in 22%, 13%, and 0.4% of patients, respectively. The incidence of grade ≥ 3 neuropathy was higher among patients with baseline neuropathy by FACT/GOG-Ntx questionnaire compared with patients without baseline neuropathy (14% v 4%, respectively). In all 256 patients, neuropathy led to dose reduction in 12% and discontinuation in 5%. Of 35 patients with neuropathy ≥ grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%.

Conclusion

Bortezomib-associated peripheral neuropathy seemed reversible in the majority of patients after dose reduction or discontinuation. Although severe neuropathy was more frequent in the presence of baseline neuropathy, the overall occurrence was independent of baseline neuropathy or type of prior therapy.
Combined-Modality Therapy for Clinical Stage I or II Hodgkin's Lymphoma: Long-Term Results of the European Organisation for Research and Treatment of Cancer H7 Randomized Controlled Trials
Authors: Noordijk Evert M. , Carde Patrice , Dupouy Noëlle , Hagenbeek Anton , Krol Augustinus D.G. , Kluin-Nelemans Johanna C. , Tirelli Umberto , Monconduit Mathieu , Thomas José , Eghbali Houchingue , Aleman Berthe M.P. , Bosq Jacques , Vovk Marjeta , Verschueren Tom A.M. , Pény Anne-Marie , Girinsky Théodore , Raemaekers John M.M. , Henry-Amar Michel
Published: June 2006

Purpose

In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control.

Patients and Methods

Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT.

Results

Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175).

Conclusion

A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.
Mechanism of Water Attacking on Brooker’s Merocyanine Dye and Its Effect on the Molecular and Electronic Structures: Theoretical Study
Authors: Awad Mohamed K , Abdel-Halim Shakir T
Published: June 2006

Semiempirical molecular orbital calculations have been performed to study the mechanism by which water molecules attack the highly negative oxycyclic oxygen atom of Brooker’s merocyanine 1-methyl-4-(4′-oxidostyryl)pyridinium betaine, M, to form mono-, di-, and tri-hydrated merocyanine complexes. In the case of mono- and di-hydrated complexes, one or two water molecules attack the oxygen atom, respectively, but in the case of the tri-hydrated complex, only two water molecules attack the oxygen atom of M with sp2 hybridization, while the third one forms a H-bond with either one of the oxygen atoms of the coordinated water molecules. The effect of H-bond formation on the molecular and electronic structures of merocyanine is investigated using the atom superposition and electron delocalization molecular orbital (ASED-MO) theory. The calculations show that the hydrated complexes are shifted towards the benzenoid valence structures in the ground state, but shifted towards quinonoid ones upon excitation. On the basis of the calculated charge distribution over the whole skeleton of the complexes, it is found that the dipole moments of the complexes are slightly affected by H-bond formation in the ground state, but strongly decrease upon excitation. The formation of hydrated merocyanine complexes are highly exothermic, downhill reactions, which is explained with respect to the stabilization of the HOMO and oxygen lone-pair levels. We believe that the attacking by water with acidic character on the basic site oxygen atom of merocyanine is a kind of acid–base interaction.
Synthesis and Characterization of Polydentate Schiff-Base Ligands and Their Complexes
Authors: Demirelli Havva , Tümer Mehmet , Gölcü Aysegül
Published: June 2006

In this study, we synthesized the amine compounds 2-{(E)-[(2-aminoethyl)imino]methyl}phenol (H3A) and 2-{(E)-[(3-aminopropyl)imino]methyl}-6-methoxyphenol (H3B) as the starting materials. From reactions of the starting materials with 2-hydroxy-5-methylisophthalaldehyde, phthalaldehyde, and 2-hydroxy-5-t-butylisophthalaldehyde, we prepared the new ligands H3L1–H3L3 and H2L. The Cu(II) and Cd(II) complexes of the ligands have been obtained. Microanalytical data, magnetic moment, 1H(13C) NMR, mass spectra, FT-IR, and conductivity measurements have been used to explain the structures of the ligands and their complexes. The protonation constants of the ligands H3L1–H3L3 have been studied in a 1:1 molar ratio (M:L). Protonation and stability constants of the Schiff bases and their Cu(II) and Cd(II) complexes have been determined by the potentiometric titration method in 50% dioxane–water media at 25.00 ± 0.02 °C under a nitrogen atmosphere and ionic strength of 0.1 M NaClO4. The ligands H3L1–H3L3 have seven protonation constants. In other words, the ligand H2L has six protonation constants. The variation of protonation constants of these compounds were interpreted on the basis of structural effects exposed by the substituents.
197Au Mössbauer Spectroscopic Study of Binuclear Cycloaurated Complexes Containing Bridging (2-Diphenylarsino-n-methyl)phenyl (n = 5 and 6)
Authors: Kitadai Kunihiko , Takahashi Masashi , Takeda Masuo , Bhargava Suresh K , Bennett Martin A
Published: June 2006

197Au Mössbauer spectra have been measured on a series of binuclear gold complexes containing a bridging As–C ligand. The plot of quadrupole splitting (Q.S.) against isomer shift (I.S.) indicates that the gold–arsenic bond in these complexes is less covalent than the gold–phosphorus bond in analogous P–C complexes.
Synthesis and Spectral Properties of Fluorescent Dithienylmaleimides
Authors: Shirinian Valerii Z , Krayushkin Mikhail M , Nabatov Boris V , Kuznetsova Ol’ga Yu , Shimkin Alexey A
Published: June 2006

A convenient preparative method of the synthesis of dithienylethenes based on maleimides was proposed. Previously, difficult accessible dithienylethene derivatives, in which 2-thienyl substituents are attached to the double bond of maleimide, have been synthesized. The spectral properties of the dithienylmaleimides were studied and it has been shown that these compounds do not belong to photochromes but they possess fluorescent properties.
Phenalenyl-Based Highly Conductive Molecular Systems with Hydrogen-Bonded Networks: Synthesis, Physical Properties, and Crystal Structures of 1,3- and 1,6-Diazaphenalenes, and Their Protonated Salts and Charge-Transfer Complexes with TCNQ
Authors: Murata Tsuyoshi , Morita Yasushi , Fukui Kozo , Tamaki Koichi , Yamochi Hideki , Saito Gunzi , Nakasuji Kazuhiro
Published: June 2006

Protonated salts and charge-transfer complexes of the 1,3- and 1,6-diazaphenalene (DAP) systems 5–7 have been investigated for new conducting molecule-based materials. Cyclic voltammetry measurements revealed that DAP derivatives are stronger electron donors than hydroquinone, and some of them possess comparable electron-donating abilities to TTF. X-ray crystal structure analyses of HX (X = Br− and BF4−) salts of 5b, 5c, and 6e confirmed their one-dimensional structures by N–H···X···H–N hydrogen bonds and their ability to form hydrogen-bonded networks in charge-transfer complexes. Actually, in the TCNQ salts of protonated 5c·H+ and 7b·H+, N–H···N≡C hydrogen-bonding interactions between DAP molecules and TCNQ molecules constructed a characteristic hydrogen-bonded cyclic tetramer and linear D–A–D triad, respectively. On the other hand, TCNQ complexes of 1,3- and 1,6-DAP derivatives, prepared by a conventional mixing method of each neutral component, were found to be partial charge-transfer complexes with segregated stacking columns as elucidated from IR and electronic spectra. Their compressed pellets exhibited high electrical conductivity (10−2–10−1 S cm−1) at room temperature with semiconducting behavior (activation energy, Ea = 40–80 meV).
Structure Elucidation of Briarane Diterpenoids Using Molecular Mechanics Calculations
Authors: Uchio Yasuto , Kubota Natsuki K , Haino Takeharu , Fukazawa Yoshimasa
Published: June 2006

A combination of NMR analysis and molecular mechanics calculations has succeeded in the determination of the stereostructure of flexible briarane diterpenoids. The molecular mechanics calculations disclosed the multi-conformational nature of the briarane diterpenoids and gave a successful reproduction of the observed 3J coupling constants to give the correct relative configuration of each stereogenic center in these molecules. An X-ray crystallographic study of these diterpenoids supports the reliable performance of the structure elucidation of these compounds.
Total Synthesis of Stevastelins: Structure Confirmation of Stevastelins B and B3, and Structure Revision of Stevastelin C3
Authors: Kurosawa Kazuo , Matsuura Keigo , Nagase Toshihiko , Chida Noritaka
Published: June 2006

The total syntheses of stevastelins B, B3, C3, and the 5-deoxy derivative of stevastelin C3, novel cyclic depsipeptides starting from l-quebrachitol, and amino acids are described. Stereoselective introduction of two methyl groups into l-quebrachitol, followed by regioselective cleavage of the cyclohexane ring by way of the Baeyer–Villiger reaction effectively afforded the fatty acid moiety of stevastelins. Introduction of the peptide and subsequent macrolactamization gave stevastelin B. Stevastelins C3 and B3 were also synthesized by a similar way. The direct comparison of synthetic stevastelins with natural compounds revealed that the synthetic stevastelins B and B3 are identical to the natural products, confirming the proposed structures. However, the synthetic stevastelin C3 was found to not be identical with the natural product. To elucidate the structure of stevastelin C3, degradation of the natural product was carried out to show the possibility that the natural product could be a 5-deoxy derivative of the proposed structure. Thus, the 5-deoxy derivative of the fatty acid moiety was prepared and transformed into a macrocycle. The synthetic 5-deoxy compound was fully identical to natural stevastelin C3. Based on these studies, it was shown that the structure of stevastelin C3 should be revised.
Effect of Water Molecules on the Cycloaromatization of Non-Conjugated Aromatic Tetraynes
Authors: Kawano Tomikazu , Inai Hiroki , Miyawaki Kazuhiro , Ueda Ikuo
Published: June 2006

Cycloaromatization of the thienyl tetrayne 1, which was prepared in several steps from bis(trimethylsilyl)butadiyne and 3-bromothiophene-2-carbaldehyde, in benzene (0.33 mM) in the presence of molecular sieves 3A at room temperature gave the indeno[2,1-b]thiophene ring-fused 1H-2-benzopyran derivative 10 and indeno[2,1-b]thiophene derivative 11 in 11 and 40% yields, respectively. In contrast, cycloaromatization of 1 in the presence of water molecules at room temperature gave the indeno[2,1-b]thiophene ring-fused 1H-2-benzopyran derivative 10 and the indene ring-fused indeno[2,1-b]thiophene derivative 12 in 82 and 14% yields, respectively. Cycloaromatization of the phenyl tetrayne 9 in the presence of water molecules at room temperature also resulted in a dramatic change in product yields.
N,N-Bis(4-{5-[N,N-bis(4-methoxyphenyl)-N-yloammonio]-2-methylstyryl}phenyl)ammoniumyl Triradical: A Trimer Model of High-Spin Poly[(4-methoxyphenyl-N-yloammonio)-1,2(or 4)-phenylenevinylene-1,2(or 4)-phenylene]
Authors: Fukuzaki Eiji , Abe Shigemoto , Nishide Hiroyuki
Published: June 2006

Hyperbranched poly[(4-methoxyphenyl-N-yloammonio)-1,2(or 4)-phenylenevinylene-1,2(or 4)-phenylene], obtained by the polycondensation of N-(4-methoxyphenyl)-N-(4-vinylphenyl)-3-bromo-4-vinylaniline and the subsequent oxidation, three-directionally satisfied the non-Kekulé-type π-conjugation and ferromagnetic connectivity of the unpaired electrons of triarylammoniumyl cationic radicals, and behaved as a high-spin organic polymer even at room temperature. The trimer model compound, N-(4-{5-[N,N-bis(4-methoxyphenyl)amino]-2-methylstyryl}-3-methylphenyl)-N-(4-{5-[N,N-bis(4-methoxyphenyl)amino]-2-methylstyryl}phenyl)-4-methoxyaniline, was synthesized from N-(4-methoxyphenyl)-N-(4-vinylphenyl)-3-methyl-4-vinylaniline. The corresponding ammoniumyl triradical displayed an average S (spin quantum number) value of 3/2, which supported the strong spin-coupling between the unpaired electrons of the ammoniumyl radicals through the π-conjugated and branched phenylenevinylene structure. Head-to-tail linkage and the branched structure of the polymer were also studied by a model reaction of N-(4-methoxyphenyl)-N-(4-vinylphenyl)-3-methyl-4-vinylaniline and bromobenzene.
Pollination Competition Effects on Gene‐Flow Estimation: Using Regular vs. Male‐Sterile Bait Plants
Authors: Wang Junming , Yang Xiusheng , Li Yi , Elliott Phillip F.
Published: June 2006

Pollen‐mediated gene flow from transgenic crops is a concern of the scientific community as well as the general public. Although a common practice, the use of male‐sterile bait plants in field trials to demonstrate rates of gene transfer has been questioned due to the lack of pollination competition. However, little direct evidence has been published. Field experiments of male‐sterile and male‐fertile corn bait plants were conducted in 2001 and 2002, respectively, to evaluate the effects of pollination competition on gene‐flow assessment. Male‐sterile bait plants exhibited a significantly higher rate of outcrossing than male‐fertile plants. The results obtained from this study suggest that actual gene flow from transgenic plants to their wild‐type cultivars or relatives is likely to be lower than estimates reported in previous studies using male‐sterile bait plants, and that male‐fertile that is, normal, bait plants should be used in future studies attempting to estimate gene flow.
Optimum Plant Population of Bt and Non‐Bt Corn in Wisconsin
Authors: Stanger Trenton F. , Lauer Joseph G.
Published: June 2006

Bt (Bacillus thuringiensis) corn (Zea mays L.) hybrids resist European corn borer [Ostrinia nubilalis (Hübner)] damage and lodge less, creating interest among growers, agronomists, and seed companies in their yield response to increasing plant population. Corn hybrids with Bt and non‐Bt traits were evaluated from 2002 to 2004 across 10 locations in Wisconsin in 76‐cm rows at target populations from 61 750 to 123 500 plants ha−1 to (i) determine the agronomic and economic optimum plant population for corn and (ii) identify agronomic and economic optimum plant populations for Bt and non‐Bt hybrids. The quadratic model for both grain yield and grower return response to plant population was significant. The maximum yield plant population (MYPP) for Bt and non‐Bt corn was 104 500 and 98 800 plants ha−1, respectively. The overall MYPP for corn was 102 400 plants ha−1, which is 28 300 plants ha−1 more than the current Wisconsin recommendation of 74 100 plants ha−1. Planting corn to the MYPP increased grain yield by 4.2% over the current population recommendation. However, the economically optimum plant population (EOPP) for both Bt and non‐Bt corn was 83 800 plants ha−1. It was concluded that Bt corn hybrids require higher plant populations for maximizing yield potential; however the higher harvest costs related to those greater yields and the higher seed costs associated with attaining those populations resulted in no difference in the EOPP between Bt and non‐Bt corn. Plant population recommendations for corn should be near 83 800 plants ha−1, the point where the EOPP was achieved. Since this recommendation is affected by rising seed and management costs and variable market prices, a periodic evaluation of plant population response for newly released hybrids should be done.
Morphological Characteristics of Perennial Ryegrass Leaves that Influence Short‐Term Intake in Dairy Cows
Authors: Barre P. , Emile J.‐C. , Betin M. , Surault F. , Ghesquière M. , Hazard L.
Published: June 2006

In sustainable agriculture, adaptation of swards to grazing is a major issue for breeding forage grass cultivars. Understanding the relationships between sward traits and animal production under grazing could help to identify criteria for selection. Intake is the major limiting factor for animal production under grazing. In this paper, short‐term intake rate by grazing dairy cows (Bos taurus) is compared between eight diploid perennial ryegrass (Lolium perenne L.) populations. Four replicates per population were measured over four periods (April and May 2001, and April and October 2002) in two experiments per period, that is, intermediate‐ and late‐maturity groups. For each period, sward structure was characterized by tiller density, leaf blade and sheath lengths, and green leaf and total dry matter (DM) yield, while nutritive value was characterized by in vitro dry matter digestibility (IVDMD), percent of DM, N, water‐soluble carbohydrate (WSC), and neutral‐detergent fiber (NDF) contents. For the late‐maturity populations, the population with the shortest leaves had a lower fresh matter intake rate (10.5 kg h−1) than the three others (12, 12, and 11.6 kg h−1, respectively). For the intermediate‐maturity populations, differences in intake rates among populations were significant (P = 0.06) for all periods and were highly significant (P < 0.0004) in April 2002. In this period, 49% of the variation in fresh matter intake rate could be explained by blade length. In conclusion, differences in short‐term intake rate between populations of diploid perennial ryegrass are highlighted. In both maturity groups, blade length appears to be an important factor explaining these differences.