bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Symptoms of Chronic Fatigue Syndrome in a Community-Based Versus Tertiary Care Sample
Authors: Jason Leonard A. , Plioplys Audrius V. , Torres-Harding Susan , Corradi Karina
Published: August 2003

Chronic Fatigue Syndrome (CFS) is a debilitating condition characterized by six or more months of prolonged or relapsing, unexplained fatigue of new or definite onset and at least four of eight associated somatic and cognitive symptoms. Almost all studies of samples with patients with CFS have relied on referrals from physicians or health facilities. Underserved minorities, who not only tend to manifest higher levels of chronic illness, but are also less likely to seek and receive adequate medical care, have not been adequately represented in these studies. The present study compared two groups of individuals with CFS, one from a communitybased sample and another from a tertiary-based sample. Findings indicate that patients with CFS from tertiary care settings have a higher frequency of symptoms than those in the general population who have CFS.
The Role of Coping Appraisal in Reactions to Fear Appeals: Do We Need Threat Information?
Authors: Ruiter Robert A.C. , Verplanken Bas , Kok Gerjo , Werrij Marieke Q.
Published: August 2003

Fear appeal theory postulates a multiplicative relationship between threat information and coping appraisal on fear control (e.g. avoid thinking about breast cancer to reduce feelings of fear) and danger control (e.g. motivation to perform monthly breast self-examination to detect breast cancer). That is, the effects of threat information on measures of both coping modes are moderated by beliefs about one’s ability to cope with the presented threat. However, in the present study no support for an interaction between threat information and coping appraisal was found on both coping modes. Instead threat information seems to contribute positively to fear control and not to danger control, whereas coping appraisal contributed positively to danger control and negatively to fear control. The results thus suggest that we might do without threatening information in persuading peopo adopt healthpromoting behaviours.
Between Credibility and Commodification
Authors: Fürsich Elfriede
Published: August 2003

This article examines the institutional logic of programming for global audiences using Discovery Communications Inc. as an example. Global media expansion is connected to other trends such as the fragmentation of audiences, industry consolidation and greater profit expectations. One of the genres fitting these new programming demands is so-called nonfiction entertainment. The article analyzes how Discovery Communications Inc. developed this genre distinction situated between traditional journalistic values and commercial interests, and explains the problematic implications of this dynamic on independent documentary producers and public service television. Concluding, the author highlights some consequences of these findings for research in international communication and media economy.
Jon Koplo
Authors: Pausacker Helen
Published: August 2003

This essay examines the tragi-comical fictional episodes and accompanying cartoons, Ah... tenane (Oh... really), in the local newspaper, SOLOPOS. The daily lives of the fictional characters in these episodes were played out against a background of the violent mass student demonstrations and the May 1998 riots in Solo, Central Java. Within the newspaper, the characters provide a face to the crowd and give a voice to the silent majority. Their role is reminiscent of that played by the punakawan, or clowns in traditional wayang puppet theatre, who provide relief from the main narrative, fooling around while their masters are serious. This essay compares these fictional episodes both to wayang and to comic strips in other Indonesian newspapers, commenting on the changing identities of the characters, the depiction of race and gender and the interaction of fact and fiction.
Museums without a Past
Authors: dos Santos Myrian Sepúlveda
Published: August 2003

The myth of origin of each nation is a shifting cultural value, associated with a nation's ethos and sense of identity, and is contingent upon one's experience in the world. As museums have come to assume a crucial role in the building of the institutionalized notion of the past that is present in national identities, they have become privileged sites for investigation. This article examines the construction of myths of origin in 19th-century Brazilian museums and argues that the building of the Brazilian nation involved the construction of a historical sense strongly based on a future-oriented narrative of time. It focuses on the struggles for representation within the nation, as well as in some long-term processes and structures, which involve a dialogue between nations.
Media Capital
Authors: Curtin Michael
Published: August 2003

Prior studies that emphasize a one-way flow of US programming to the periphery of the world system are now being reassessed in light of the increasing volume and velocity of multi-directional media flows that emanate from particular cities, such as Bombay, Cairo, and Hong Kong. These emerging centers of transnational cultural production suggest a need to supplement the current scholarly emphasis on national media systems with a more intensive examination of media capitals. Examining the histories of Hollywood, Hong Kong, and Chicago television, this essay illustrates how scholars might use media capital as a concept that would foster empirically grounded analysis of the temporal dynamism and spatial complexity of the global media environment.
Oliver's Twist
Authors: Hollows Joanne
Published: August 2003

Despite the explosion of interest in cooking, there has been little research into the meanings that men bring to their cooking practices. This article examines how a mode of domestic masculinity is negotiated in Jamie Oliver's television shows and cookbooks. Drawing on Marjorie DeVault's work, in which she argues that cooking is a way in which women construct themselves as `recognizably womanly', the article argues that in The Naked Chef cooking is constructed as `recognizably manly' through association with `recognizable masculinities'. The construction of the masculine domestic cook involves disavowing the extent to which cooking is a form of labour and constructing it as a `fun' leisure and lifestyle activity. The article draws on Bourdieu's work to suggest that the ability to experience cooking as leisure is dependent on a distance from both economic and temporal constraints, a position that is both classed and gendered.
Children’s Perspectives on Family Literacy: Methodological Issues, Findings and Implications for Practice
Authors: Nutbrown Cathy , Hannon Peter
Published: August 2003

This article reports a study of family literacy practices from the perspectives of five-year-old children drawn from areas of social and economic deprivation in an English city. Methodological and ethical issues of interviewing young children are discussed. An interview survey ( N= 71) found literacy activity reported in all homes; fathers involved in literacy with their children; and boys (as well as girls) involved in literacy activity. Findings were compared with those of a further randomly selected sample ( N= 77) whose parents had participated in a family literacy programme. The comparison showed a modest, but consistent, increase in child-reported family literacy activity in the programme group, and concludes that the impact of a family literacy programme is discernible through children’s perspectives. Implications for family literacy practices and the need for further research, including measures of children’s literacy achievement and views of parents and the teachers participating in the programme, are identified.
How Well Suited are Electronic Books to Supporting Literacy?
Authors: de Jong Maria T. , Bus Adriana G.
Published: August 2003

This article discusses children’s picture story books on the computer (also known as e-book, CD-ROM story book, talking book, living book, interactive book, digital book, disc book or computer book). These books minimally include an oral reading of the story instead of or in addition to printed text. We put together a collection of 55 Dutch and 5 well known English electronic books that were commercially available between 1995 and 2002 for children in the age range from three to seven years. We conducted a content analysis to find out how well books currently commercially available on CD-ROM are indeed suited to supporting children’s literacy. Our coding focused on multimedia additions, interactivity of pictures and interactive legibility. Based on studies into effects of electronic books, we describe which books on CD-ROM can serve as models for parents, teachers and publishers.
Collaborative Writing and Children’s Use of Literate Language: A Sequential Analysis of Social Interaction
Authors: Jones Ithel
Published: August 2003

Research in children’s oral language and early literacy learning currently emphasizes the facilitative role of social context. This study examined the sequential interactions of first-grade students during collaborative writing to determine the ways in which peer collaboration relate to literate language use. Same gender dyads of seven- and eight-year-old children were observed during collaborative writing tasks and measures of oral language were collected. Sequential analyses of social interaction suggested that children’s use of literate language during collaborative writing tasks is related to various forms of social regulation such as offering assistance, checking, or guiding. The data support the proposition that social forms of regulation elicit literate language and self-regulation strategies. The results are discussed in terms of the role of social regulation in the context of peer collaboration.
The Multisemiotic Resources of Biliterate Children
Authors: Kenner Charmian , Kress Gunther
Published: August 2003

This article argues that children gain access to an enhanced range of communicative resources through familiarity with more than one writing system. Different scripts can be seen as different modes, giving rise to a variety of potentials for meaning-making. In case-studies of children’s responses to learning Chinese, Arabic or Spanish as well as English at the age of six, they were found to be exploring these potentials in terms of symbol design, spatial framing and directionality. A multimodal analysis shows how children can build up ‘embodied knowledges’ as they construct different visual and actional dispositions through the bilingual script-learning experience. Such flexibility is likely to be an asset in a world that makes increasing use of multilingual and multimodal communication.
Suppressor of cytokine signaling 1 attenuates IL-15 receptor signaling in CD8+ thymocytes
Authors: Ilangumaran Subburaj , Ramanathan Sheela , Ning Terry , La Rose Jose , Reinhart Brandon , Poussier Philippe , Rottapel Robert
Published: August 2003

SOCS1-/- mice die prematurely of increased interferon-γ (IFNγ) signaling with severe thymic atrophy and accelerated maturation of T cells. However, it was unclear whether the thymic defects were caused by SOCS1 deficiency or by increased IFNγ signaling. Using SOCS1-/-IFNγ-/- mice, we show in this study that SOCS1 deficiency skews thymocyte development toward CD8 lineage independently of IFNγ. Fetal thymic organ cultures and intrathymic transfer of CD4-CD8- precursors into Rag1-/- mice show that the lineage skewing in SOCS1-/- mice is a T-cell autonomous defect. Interestingly, SOCS1 is not required for attenuating interleukin-7 (IL-7) signaling at the CD4-CD8- stage but is essential for regulating IL-15 and IL-2 signaling in CD8+ thymocytes. IL-15 selectively stimulates SOCS1-/- CD8+ thymocytes, inducing sustained signal transducer and activator of transcription 5 (STAT5) phosphorylation and massive proliferation. IL-15 also strongly up-regulates Bcl-xL and CD44 in CD8+ thymocytes lacking SOCS1. The SOCS1 gene is induced in CD4+ thymocytes by γc cytokines, whereas CD8+ thymocytes constitutively express SOCS1 mRNA even in the absence of cytokine stimulation. Because many different cell types express IL-15, our results strongly suggest that SOCS1 functions as an indispensable attenuator of IL-15 receptor signaling in developing CD8+ thymocytes. (Blood. 2003;102:4115-4122)
What has been learnt fromP/Vcurves in patients with acute lung injury/acute respiratory distress syndrome
Authors: Maggiore S.M. , Richard J‐C. , Brochard L.
Published: August 2003

Mechanical impairment of the respiratory system was recognised soon after the description of acute respiratory distress syndrome. The analysis of the pressure/volume (P/V) curve of the respiratory system contributed a lot to the understanding of the pathophysiology of acute lung injury and formed the basis for lung protection. The lower and upper inflection points were regarded as points of interest to avoid cyclic derecruitment and overdistension and to optimise ventilatory settings. However, because of the heterogeneity of lung injury, reducing the mechanical properties of the whole respiratory system to a single curve is a schematic approach, which makes interpretation difficult.

New data suggest that alveolar re-inflation occurs along the wholeP/Vcurve that can, therefore, be considered as a recruitment curve. The lower inflection point has no relationship with alveolar opening and closure and does not indicate the positive end-expiratory pressure needed to prevent alveolar collapse. The shape of theP/Vcurve gives information about the extension and the homogeneity of lung injury, indicating the possibility of lung recruitment. The upper inflection point, classically seen as the beginning of overdistension, may also indicate the end of recruitment.

The pressure/volume curve offers the unique opportunity of evaluating alveolar recruitment/derecruitment at the bedside that can be helpful for the identification of optimal ventilatory settings and makes the curve a valuable tool for the ventilatory management of acute lung injury.
Ventilator-induced lung injury
Authors: Ricard J‐D. , Dreyfuss D. , Saumon G.
Published: August 2003

During mechanical ventilation, high end-inspiratory lung volume (whether it be because of large tidal volume (VT) and/or high levels of positive end-expiratory pressure) results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). Previous injury sensitises lung to mechanical ventilation.

This experimental concept has recently received a resounding clinical illustration after a 22% reduction of mortality was observed in acute respiratory distress syndrome patients whoseVThad been reduced. In addition, it has been suggested that repetitive opening and closing of distal units at low lung volume could induce lung injury but this notion has been challenged both conceptually and clinically after the negative results of the Acute Respiratory Distress Syndrome clinical Network Assessment of Low tidal Volume and Elevated end-expiratory volume to Obviate Lung Injury (ARDSNet ALVEOLI) study.

Experimentally and clinically, involvement of inflammatory cytokines in VILI has not been unequivocally demonstrated. Cellular response to mechanical stretch has been increasingly investigated, both on the epithelial and the endothelial side. Lipid membrane trafficking has been thought to be a means by which cells respond to stress failure.

Alterations in the respiratory system pressure/volume curve during ventilator-induced lung injury that include decrease in compliance and position of the upper inflection point are due to distal obstruction of airways that reduce aerated lung volume. Information from this curve could help avoid potentially harmful excessive tidal volumereduction.
Inflammatory response to infectious pulmonary injury
Authors: Delclaux C. , Azoulay E.
Published: August 2003

This review describing the inflammatory response to infectious pulmonary injury is focused on the innate immunity of the distal lung to bacterial pneumonia. The fact that the inflammatory response varies to some extent with the bacterial strain responsible for the infection is emphasised. The key cellular components present in the distal lung are described. The major role of alveolar macrophage is described, inasmuch as it responds to the usual daily challenges of bacteria entering the terminal airways and is capable of initiating an inflammatory reaction if the microbial challenge is either too large or too virulent. Under these conditions, the alveolar macrophages initiate an inflammatory response that recruits large numbers of neutrophils into the alveolar spaces.

The strategy of the innate immune response may not be to recognise every possible antigen, but rather to focus on a few, highly conserved structures present in large groups of microorganisms. These structures are referred to as pathogen-associated molecular patterns and the receptors of the innate immune system that evolved to recognise them are called pattern-recognition receptors.

The soluble factors in innate defence, such as cytokines, are described, and a last paragraph discusses whether a specific inflammatory response could characterise nosocomial pneumonia.
How respiratory system mechanics may help in minimising ventilator-induced lung injury in ARDS patients
Authors: Terragni P.P. , Rosboch G.L. , Lisi A. , Viale A.G. , Ranieri V.M.
Published: August 2003

The main supportive therapy in acute respiratory distress syndrome patients is mechanical ventilation. As with any therapy, mechanical ventilation has side-effects, and may induce lung injury (ventilator-induced lung injury (VILI)/ventilator-associated lung injury). The mechanical factors responsible for VILI are thought to be related to tidal recruitment/derecruitment of previously collapsed alveoli and/or pulmonary overdistension.

The volume/pressure (V/P) curve of the respiratory system in patients as well as in animal models of acute lung injury (ALI) has a characteristic sigmoid shape, with a lower inflection point (LIP) corresponding to the pressure/end-expiratory volume required to initiate recruitment of collapsed alveoli, and an upper inflection point (UIP) corresponding to the pressure/end inspiratory volume at which alveolar overdistension occurs. “Protective” ventilatory approaches have therefore set out to minimise mechanical injury by using theV/Pcurve to individualise positive end-expiratory pressure (PEEP) (PEEP above the LIP) and tidal volume (by setting end-inspiratoryV/Pbelow the UIP) since a large number of experimental studies correlateP/Vcurves to histological and biological manifestations of VILI and two randomised trials showed that protective ventilatory strategy individually tailored to theP/Vcurve minimised pulmonary and systemic inflammation and decreased mortality in patients with ALI.

However, despite the fact that several studies have: 1) proposed new techniques to perform pressure/volume curves at the bedside, 2) confirmed that the lower inflection point and upper inflection point correspond to computed tomography scan evidence of atelectasis and overdistension, and 3) demonstrated the ability of the pressure/volume curve to estimate alveolar recruitment with positive end-expiratory pressure, no large studies have assessed whether such measurement can be performed in all intensive care units as a monitoring tool to orient ventilator therapy. Preliminary experimental and clinical studies show that the shape of the dynamic inspiratory pressure/time profile during constant flow inflation (stress index), allows prediction of a ventilatory strategy that minimises the occurrence of ventilator-induced lung injury.
Pressure/volume curves and lung computed tomography in acute respiratory distress syndrome
Authors: Rouby J‐J. , Lu Q. , Vieira S.
Published: August 2003

Pressure/volume (P/V) curves can be measured by static methods, constant or sinusoidal flow methods and the dynostatic method that allows a breath-to-breath determination ofP/Vcurves. Recent ventilators are equipped with specific flow generators and software aimed at obtainingP/Vcurves without disconnecting the patient from the ventilator.

The most recent generation of computed tomography scanners allows the quantitative determination of lung aeration, lung volumes (gas and tissue), alveolar recruitment and lung overinflation of the whole lung. In the supine position, the acute respiratory distress syndrome (ARDS) lung is characterised by an increase in lung tissue that predominates in upper lobes and a massive loss of aeration that predominates in lower lobes.

In a minority of ARDS patients, the loss of aeration is homogeneously distributed. The overall lung volume of upper lobes is preserved suggesting an alveolar flooding-induced loss of aeration. In contrast, the overall lung volume of lower lobes is reduced because the heart and the abdomen exert an external compression that contributes to the loss of aeration. TheP/Vcurve is a lung recruitment curve and the chord compliance indicates the potential for recruitment. In such patients, alveolar recruitment resulting from positive end-expiratory pressure is not accompanied by lung overinflation.

In a majority of acute respiratory distress syndrome patients, upper lobes remain partially or totally aerated despite a marked regional increase in lung tissue. The upper lobes' overall lung volume is either normal or increased, suggesting that the lung does not collapse under its own weight as generally believed. In lower lobes, the overall lung volume is reduced because the heart and the abdomen exert an external compression that contributes to the loss of aeration. The pressure/volume curve is influenced by the recruitment of poorly and nonaerated lung regions and by the mechanical properties of the part of the lung remaining aerated. In such patients, alveolar recruitment resulting from positive end-expiratory pressure >10 cmH2O is preceded and accompanied by lung overinflation.
Recruitment manoeuvres in acute lung injury/acute respiratory distress syndrome
Authors: Morán I. , Zavala E. , Fernández R. , Blanch L. , Mancebo J.
Published: August 2003

Acute respiratory distress syndrome/acute lung injury is characterised by profound hypoxaemia due to a permeability pulmonary oedema.

In this setting, recruitment manoeuvres (RMs) can be a useful tool as adjuncts to lung protective ventilatory strategies to prevent cyclic alveolar stress and avoid alveolar collapse.

Many experimental and physiological studies have discussed the use of RMs but only a few heterogeneous clinical experiences have demonstrated the beneficial and deleterious effects that can occur using these manoeuvres. Besides, a lot of questions remain to be answered to find the best way to perform optimal RMs.

Further experimental and clinical trials are needed to understand the potential beneficial effects of recruitment manoeuvres when using a protective mechanical ventilation strategy. This paper is a general review of experimental works that support application of recruitment manoeuvres emphasising the clinical studies that have been published to date in acute respiratory distress syndrome patients.
The issue of dynamic hyperinflation in acute respiratory distress syndrome patients
Authors: Vieillard-Baron A. , Jardin F.
Published: August 2003

Dynamic hyperinflation is produced by a diffuse expiratory flow limitation impairing exhalation under mechanical ventilation. It constitutes a serious clinical problem in patients exhibiting bronchial asthma or chronic obstructive pulmonary disease, when mechanical ventilation is required. But this phenomenon may also complicate respiratory support in acute respiratory distress syndrome (ARDS) patients.

The presence of diffuse airflow limitation in ARDS patients has sometimes been noticed in the past, but its consequences have only recently been emphasised in a dynamic study, using bedside recording of flow/volume loops during respiratory support.

More recently, by recording systematically a prolonged expiration, the current authors have observed a localised airflow limitation in a majority of ARDS patients, constituting another potential factor of dynamic hyperinflation under respiratory support. In the same report, the current authors' have emphasised the impact of this limitation on the shape of the pressure/volume loop.

At a time when increasing respiratory support is proposed to improve carbon dioxide clearance in acute respiratory distress syndrome submitted to protective ventilation, dynamic hyperinflation may become a major clinical problem in this setting.
Pulmonary and extrapulmonary acute respiratory distress syndrome are different
Authors: Pelosi P. , D'Onofrio D. , Chiumello D. , Paolo S. , Chiara G. , Capelozzi V.L. , Barbas C.S.V. , Chiaranda M. , Gattinoni L.
Published: August 2003

Acute respiratory distress syndrome (ARDS) can be derived from two pathogenetic pathways: a direct insult on lung cells (pulmonary ARDS (ARDSp)) or indirectly (extrapulmonary ARDS (ARDSexp)). This review reports and discusses differences in biochemical activation, histology, morphological aspects, respiratory mechanics and response to different ventilatory strategies between ARDSp and ARDSexp. In ARDSp the direct insult primarily affects the alveolar epithelium with a local alveolar inflammatory response while in ARDSexp the indirect insult affects the vascular endothelium by inflammatory mediators through the bloodstream.

Radiological pattern in ARDSp is characterised by a prevalent alveolar consolidation while the ARDSexp by a prevalent ground-glass opacification. In ARDSp the lung elastance, while in ARDSexp the chest wall and intra-abdominal chest elastance are increased. The effects of positive end-expiratory pressure, recruitment manoeuvres and prone position are clearly greater in ARDSexp.

Although these two types of acute respiratory distress syndrome have different pathogenic pathways, morphological aspects, respiratory mechanics, and different response to ventilatory strategies, at the present, is still not clear, if this distinction can really ameliorate the outcome.
Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS
Authors: Meduri G.U. , Carratu P. , Freire A.X.
Published: August 2003

Acute respiratory distress syndrome (ARDS) is a disease of multifactorial etiology characterised by rapid development of severe diffuse and nonhomogenous inflammation of the pulmonary lobules causing life-threatening hypoxaemic respiratory failure. The current authors tested a therapeutic intervention on a previously defined pathophysiological model of ARDS. The model was defined by investigating, during the natural history of ARDS, the relationship among the three fundamental elements of a disease process pathogenesis, structural alterations, and functional consequences. In these studies, the present authors provided biological and morphological evidence indicating that ARDS patients failing to improve after 1 week of mechanical ventilation (unresolving ARDS) have intense and protracted (dysregulated) pulmonary and systemic inflammatory and neo-fibrogenetic activity.

Nuclear factor-κB and the glucocorticoid receptor have diametrically opposed functions in regulating inflammation. This chapter will review recent data indicating that poor outcome in acute respiratory distress syndrome might be related in part to failure of the activated glucocorticoid receptors to downregulate the transcription of inflammatory cytokines despite elevated levels of circulating cortisol. In a small randomised study of patients with unresolving acute respiratory distress syndrome, the current authors have shown that prolonged glucocorticoid supplementation improved all aspects of glucocorticoid receptors function and enhanced glucocorticoid-mediated anti-inflammatory action by interfering with nuclear factor-κB activation.
New advances in the use of noninvasive ventilation for acute hypoxaemic respiratory failure
Authors: Antonelli M. , Pennisi M.A. , Conti G.
Published: August 2003

Noninvasive ventilation (NIV) includes various techniques for augmenting alveolar ventilation without an endotracheal airway. The theoretical advantages of this approach include avoiding the complications associated with endotracheal intubation, improving patient comfort, preserving airway defence mechanisms, speech and swallowing.

The successful application of NIV in hypoxaemic acute respiratory failure (ARF) of varied etiologies has been extensively described but success rate is strictly dependent on ARF etiology and until today the application of NIV strategies in the setting of hypoxaemic ARF is controversial. Larger, controlled studies are required to clarify the role of NIV in the setting of hypoxaemic ARF.

The correct choice of the patient ventilator interface is a crucial issue in noninvasive ventilation. The study of new interfaces could improve tolerability reducing the noninvasive ventilation failure rate.
Diagnosis and treatment of nosocomial pneumonia in ALI/ARDS patients
Authors: Fagon J‐Y. , Chastre J.
Published: August 2003

Ventilator-associated pneumonia (VAP) is a common complication of the acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), often leading to the development of sepsis, multiple organ failure, and death. However, the diagnosis of pulmonary infection in patients with ARDS/ALI is often difficult: the systemic signs of infection, such as fever, tachycardia, leukocytosis are nonspecific findings in such patients; a variety of causes other than pneumonia can explain asymmetric consolidation in patients with ARDS and marked asymmetry of radiographic abnormalities has also been reported in patients with uncomplicated ARDS.

In 2003, physicians in charge of these patients have to identify patients with true bacterial lung infection, to select appropriate initial antibiotic therapy, to adjust therapy as soon as possible, and to withhold antibiotics in patients without VAP. To do that, a bacteriological strategy based on the use of quantitative cultures of specimen obtained with fibreoptic bronchoscopy performed before initiation or modification of antibiotic treatment seems better than a strategy based on clinical evaluation alone, lowering antibiotic consumption and improving outcome. When bronchoscopy is not available or contraindicated, a nonbronchoscopic strategy or a clinical strategy with re-evaluation 3 days after initiation of treatment may be used.

Antimicrobial treatment of VAP is a complex issue. Some general principles can be helpful for the selection of initial treatment: knowledge of most frequently identified responsible pathogens and their susceptibility patterns in the unit; prior duration of hospitalisation; previously prescribed antibiotics; information obtained by direct examination of pulmonary secretions; antibacterial activity and pharmacodynamic characteristics of antibiotics that could be used to treat this infection.

Appropriateness of initial antimicrobial therapy is probably a major prognostic factor for patients with ventilator-associated pneumonia. Thus, before new antiboitics are administered, reliable pulmonary specimens must be obtained for direct examination and cultures.
CHOP Compared With CHOP Plus Granulocyte Colony-Stimulating Factor in Elderly Patients With Aggressive Non-Hodgkin’s Lymphoma
Authors: Doorduijn J.K. , van der Holt B. , van Imhoff G.W. , van der Hem K.G. , Kramer M.H.H. , van Oers M.H.J. , Ossenkoppele G.J. , Schaafsma M.R. , Verdonck L.F. , Verhoef G.E.G. , Steijaert M.M.C. , Buijt I. , Uyl-de Groot C.A. , van Agthoven M. , Mulder A.H. , Sonneveld P.
Published: August 2003

Purpose: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin’s lymphoma (NHL).

Patients and Methods: Patients aged 65 to 90 years (median, 72 years) with stage II to IV aggressive NHL were randomly assigned to receive standard CHOP every 3 weeks or CHOP plus G-CSF every 3 weeks on days 2 to 11 of each cycle.

Results: In 389 eligible patients, the relative dose intensities (RDIs) of cyclophosphamide (median, 96.3% v 93.9%; P = .01) and doxorubicin (median, 95.4% v 93.3%; P = .04) were higher in patients treated with CHOP plus G-CSF. The complete response rates were 55% and 52% for CHOP and CHOP plus G-CSF, respectively (P = .63). The actuarial overall survival at 5 years was 22% with CHOP alone, compared with 24% with CHOP plus G-CSF (P = .76), with a median follow-up of 33 months. Patients treated with CHOP plus G-CSF had an identical incidence of infections, with World Health Organization grade 3 to 4 (34 of 1,191 cycles v 36 of 1,195 cycles). Only the cumulative days with antibiotics were fewer with CHOP plus G-CSF (median, 0 v 6 days; P = .006) than with CHOP alone. The number of hospital admissions and the number of days in hospital were not different.

Conclusion: In elderly patients, G-CSF improved the RDI of CHOP, but this did not lead to a higher complete response rate or better overall survival. G-CSF did not prevent serious infections.
Phase I Trial of Preoperative Concurrent Doxorubicin and Radiation Therapy, Surgical Resection, and Intraoperative Electron-Beam Radiation Therapy for Patients With Localized Retroperitoneal Sarcoma
Authors: Pisters Peter W.T. , Ballo Matthew T. , Fenstermacher Mark J. , Feig Barry W. , Hunt Kelly K. , Raymond Kevin A. , Burgess Michael A. , Zagars Gunar K. , Pollock Raphael E. , Benjamin Robert S. , Patel Shreyaskumar R.
Published: August 2003

Purpose: The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS).

Patients and Methods: Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy).

Results: Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections.

Conclusion: Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.
Durable Remissions of Myelodysplastic Syndrome and Acute Myeloid Leukemia After Reduced-Intensity Allografting
Authors: Taussig D.C. , Davies A.J. , Cavenagh J.D. , Oakervee H. , Syndercombe-Court D. , Kelsey S. , Amess J.A.L. , Rohatiner A.Z.S. , Lister T.A. , Barnett M.J.
Published: August 2003

Purpose: To evaluate the use of reduced-intensity (RI) conditioning with allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Patients and Methods: Sixteen patients (median age, 54 years; range, 37 to 66 years) underwent RI-HSCT using a conditioning regimen of fludarabine 25 mg/m2 daily for 5 days and either cyclophosphamide 1 g/m2 daily for 2 days (14 patients) or melphalan 140 mg/m2 for 1 day (two patients). The median number of CD34+ cells and CD3+ cells infused per kilogram of recipient weight was 4.5 × 106 (range, 1.8 to 7.3 × 106 cells) and 2.9 × 108 (range, 0.1 to 9.6 × 108 cells), respectively.

Results: There was no transplant-related mortality (TRM) within 100 days of HSCT. Grade 1 to 2 acute graft-versus-host disease (GVHD) occurred in three patients, but neither grade 3 nor grade 4 disease was observed. Chronic GVHD occurred in 10 patients. One patient had cytomegalovirus (CMV) reactivation but did not develop CMV disease. With a median follow-up of 26 months (range, 15 to 45 months), 11 patients are alive (nine in continuous complete remission and one in complete remission after a second transplantation), and five have died (four from disease progression and one from bone-marrow aplasia induced by cyclosporine withdrawal). The 2-year actuarial overall and event-free survival rates were 69% (95% confidence interval [CI], 40% to 86%) and 56% (95% CI, 30% to 68%), respectively.

Conclusion: This strategy of RI-HSCT resulted in reliable engraftment with low incidence of acute GVHD and TRM. Durable remissions were observed in patients with MDS and AML consistent with a graft-versus-leukemia effect.
Randomized Study of High-Dose and Low-Dose Interleukin-2 in Patients With Metastatic Renal Cancer
Authors: Yang James C. , Sherry Richard M. , Steinberg Seth M. , Topalian Suzanne L. , Schwartzentruber Douglas J. , Hwu Patrick , Seipp Claudia A. , Rogers-Freezer Linda , Morton Kathleen E. , White Donald E. , Liewehr David J. , Merino Maria J. , Rosenberg Steven A.
Published: August 2003

Purpose: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens.

Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned.

Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P = .048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P = .033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P = .04).

Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.
Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer
Authors: Rödel Claus , Grabenbauer Gerhard. G. , Papadopoulos Thomas , Hohenberger Werner , Schmoll Hans-Joachim , Sauer Rolf
Published: August 2003

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer.

Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors.

Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery.

Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.
Zoledronic Acid Versus Placebo in the Treatment of Skeletal Metastases in Patients With Lung Cancer and Other Solid Tumors: A Phase III, Double-Blind, Randomized Trial—The Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group
Authors: Rosen Lee S. , Gordon David , Tchekmedyian Simon , Yanagihara Ronald , Hirsh Vera , Krzakowski M. , Pawlicki M. , de Souza Paul , Zheng Ming , Urbanowitz Gladys , Reitsma Dirk , Seaman John J.
Published: August 2003

Purpose: To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer.

Patients and Methods: Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE.

Results: Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P = .127 and P = .023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P = .023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P = .017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting.

Conclusion: Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.
Conditional Survival of Patients With the Four Major Histologic Subgroups of Lung Cancer in Denmark
Authors: Skuladottir Halla , Olsen Jørgen H.
Published: August 2003

Purpose: The survival probability of patients with lung cancer is usually based on the extent of disease as assessed at the time of diagnosis. The discouraging 5-year survival is often reported (< 10%) without taking into account changes in the survival probability as time advances from diagnosis.

Patients and Methods: Conditional survival estimates by sex, age, extent of disease, and histology were estimated for patients diagnosed with lung cancer in Denmark from 1943 to 1997. Survival probabilities were calculated by the Kaplan-Meier method, and cumulative survival estimates were used to derive conditional survival estimates.

Results: For every additional year survived, the probability of surviving the next 5 years increases from 33% (men) and 36% (women) after the first year, to 60% (men) and 67% (women) who have survived 5 years. The 5-year survival probability of patients younger than 49 years who had survived the first year was 33%, and increased to 81% after the fifth year. Corresponding estimates for 60- to 69-year-old patients were 23% and 52%. The conditional survival differed greatly among patients with localized and regional disease (29% and 10%, respectively) in the first year, but converged with time (52% and 47%, respectively) after 5 years. The conditional survival is similar in patients with squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma, but is markedly lower in patients with small-cell carcinoma.

Conclusion: For patients who have survived more than 1 year, the conditional survival probability provides a more accurate estimate of survival as compared with the conventional observed survival rates.
Can Patients With Relapsed, Previously Untreated, Stage I Epithelial Ovarian Cancer Be Successfully Treated With Salvage Therapy?
Authors: Kolomainen Desiree F. , A’Hern Roger , Coxon Fareeda Y. , Fisher Cyril , King D. Michael , Blake Peter R. , Barton Desmond P.J. , Shepherd John H. , Kaye Stanley B. , Gore Martin E.
Published: August 2003

Purpose: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse.

Patients and Methods: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment.

Results: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients’ original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS).

Conclusion: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.