bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between exercise desaturation and pulmonary haemodynamics in COPD patients
Authors: Christensen C.C. , Ryg M.S. , Edvardsen A. , Skjønsberg O.H.
Published: September 2004

Pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD) has traditionally been explained as an effect of hypoxaemia. Recently, other mechanisms, such as arterial remodelling caused by inflammation, have been suggested. The aim of this study was to investigate whether exercise-induced PH (EIPH) could occur without concurrent hypoxaemia, and whether exercise-induced hypoxaemia (EIH) was regularly accompanied by increased pulmonary artery pressure or pulmonary vascular resistance index (PVRI).

Pulmonary haemodynamics in 17 patients with COPD of varying severity, but with no or mild hypoxaemia at rest, were examined during exercise equivalent to the activities of daily living (ADL) and exhaustion.

EIPH occurred in 65% of the patients during ADL exercise. Pulmonary arterial pressure during exercise was negatively correlated with arterial oxygen tension, but EIPH was not invariably accompanied by hypoxaemia. Conversely, EIPH was not found in all patients with EIH. The resting PVRI was negatively correlated with arterial oxygen tension during ADL exercise, but an elevated PVRI without EIH occurred in 35% of the patients.

In conclusion, exercise-induced pulmonary hypertension occurred during exercise equivalent to the activities of daily living in chronic obstructive pulmonary disease patients with no or mild hypoxaemia at rest. Although pulmonary artery pressure and arterial oxygen tension were negatively correlated during exercise, a consistent relationship between hypoxaemia and pulmonary hypertension could not be demonstrated. This may indicate that mechanisms other than hypoxaemia contribute significantly in the development of pulmonary hypertension in these patients.
Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin
Authors: Cavalher-Machado S.C. , de Lima W. Tavares , Damazo A.S. , de Frias Carvalho V. , Martins M.A. , e Silva P.M.R. , Sannomiya P.
Published: September 2004

Hormones play a modulating role in allergic inflammation. An inverse relationship between atopy and diabetes mellitus was reported. The mechanisms regulating this interaction are not completely understood. This study examined whether insulin influences mast cell activation following antigen challenge in rats.

The experimental design included alloxan-induced diabetic rats and matching controls. Experiments were performed 30 days after alloxan injection. The animals were sensitised bys.c.injection of ovalbumin (OA) and aluminium hydroxide. OA-induced airway contraction, morphometric analysis of airway mast cells and tissue histamine quantification were evaluated in the isolated main bronchus and intrapulmonary bronchus upon exposure to antigenin vitro.

Relative to controls, a reduced contraction to OA was observed in bronchial segments isolated from diabetic rats. This was accompanied by a 50% reduction in the number of degranulated mast cells and in histamine release. A complete recovery of the impaired responses was observed under the influence of insulin.

In conclusion, the data suggested that insulin might modulate the controlling of mast cell degranulation; therefore, the early-phase response to antigen provocation, which represents a new insight into a better understanding of the mechanisms, accounted for the decreased risk of asthma among type-1 diabetic patients.
Bench testing of auto-adjusting positive airway pressure devices
Authors: Abdenbi F. , Chambille B. , Escourrou P.
Published: September 2004

Continuous positive airway pressure devices are routinely used to treat sleep breathing disorders. Automated devices that adjust the therapeutic pressure have recently been proposed. The utility of such devices is still controversial, as rigorous clinical comparisons are difficult to perform as a result of patient and device differences.

The current authors studied automated devices in a respiratory model that was able to mimic upper airway mechanics and to interact with pressure adjustment in a closed loop. Five auto-adjusted devices were submitted to this model, in order to determine their ability to detect respiratory events and adjust pressure accordingly.

All apnoeas were suppressed, whilst the reaction to repetitive hypopnoeas was dependent on the airflow shape. In some devices, repetitive hypopnoeas were changed to flow limitation. Artificial snoring caused a pressure increase in four devices, and constant mask leak was not systematically compensated. Only one device did not raise pressure in response to central apnoeas with opened upper airways. These findings show that, in some devices, event classification failed and normal airflow was not fully restored, resulting in elevated residual event indices.

In conclusion, this model is useful in order to reproducibly compare diagnostic and therapeutic capacities of commercial devices as a first step, before costly clinical studies.
Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions
Authors: Kikuchi E. , Yamazaki K. , Sukoh N. , Kikuchi J. , Asahina H. , Imura M. , Onodera Y. , Kurimoto N. , Kinoshita I. , Nishimura M.
Published: September 2004

The usefulness of endobronchial ultrasonography (EBUS) with guide-sheath (GS) as a guide for transbronchial biopsy (TBB) for diagnosing peripheral pulmonary lesions (PPL)s and for improving diagnostic accuracy was evaluated in this study.

EBUS-GS-guided TBB was performed in 24 patients with 24 PPLs of ≤30 mm in diameter (average diameter=18.4 mm). A 20-MHz radial-type ultrasound probe, covered with GS was insertedviaa working bronchoscope channel and advanced to the PPL in order to produce an EBUS image. The probe with the GS was confirmed to reach the lesion by EBUS imaging and X-ray fluoroscopy. When the lesion was not identified on the EBUS image, the probe was removed and a curette was used to lead the GS to the lesion. After localising the lesion, the probe was removed, and TBB and bronchial brushing were performedviathe GS.

Nineteen peripheral lesions (79.2%) were visualised by EBUS. All patients whose PPLs were visible on EBUS images subsequently underwent an EBUS-GS-guided diagnostic procedure. A total of 14 lesions (58.3%) were diagnosed. Even when restricted to PPLs <20 mm in diameter, the diagnostic sensitivity was 53%.

In conclusion, endobronchial ultrasonography with guide sheath-guided transbronchial biopsy was feasible and effective for diagnosing peripheral pulmonary lesions.
HRCT lung abnormalities are not a surrogate for exercise limitation in bronchiectasis
Authors: Edwards E.A. , Narang I. , Li A. , Hansell D.M. , Rosenthal M. , Bush A.
Published: September 2004

In paediatric bronchiectasis, there has been limited work on the relationship between disease severity as assessed by exercise limitation and high resolution computed tomography (HRCT).

An observational study was performed on 36 children who completed a questionnaire, physical examination, spirometry and sputum analysis, followed by a low dose of radiation protocol chest computed tomography (CT) scan and cycle ergometry incremental exercise test. A modified Bhalla score was used to score the HRCT abnormalities. The exercise variables used to assess functional status were heart rate, oxygen consumption, oxygen saturations and time of exercise. The results were compared with established normal paediatric values.

The median (range) age of the children was 13 yrs (10.6–17.1). Age, sex, height, weight or pubertal status were equally distributed between the children with cystic fibrosis (CF) or non-CF bronchiectasis. The children with non-CF bronchiectasis had a lower median forced expiratory volume in one second % predicted than the children with CF (69%versus76%, respectively). The distribution of lung disease differed between the two groups. The children with CF bronchiectasis had predominantly right upper lobe disease, and scored higher for the presence and extent of bronchiectasis. Otherwise, there was no statistical difference in the overall CT score or the individual CT parameters between the groups. There was evidence of exercise limitation in both CF and non-CF bronchiectasis compared to normal children. No consistent relationships were identified between the lung function parameters, HRCT findings or exercise parameters in either disease group.

In this study, high resolution computed tomography features were not found to be markers of exercise capacity. As spirometry, high resolution computed tomography features and exercise testing give different information in children with cystic fibrosis and non-cystic fibrosis bronchiectasis, the current authors suggest all three may be required for the comprehensive assessment of respiratory status.
Cost-effectiveness of full-course oral levofloxacin in severe community-acquired pneumonia
Authors: Wasserfallen J-B. , Erard V. , Cometta A. , Calandra T. , Lamy O.
Published: September 2004

Oral levofloxacin is as efficient as sequential antibiotic treatment in community-acquired pneumonia (CAP). The current authors assessed whether oral levofloxacin treatment of patients with severe CAP, followed-up for 30 days, would save money.

Over a 12-month period, 129 hospitalised patients with severe non-intensive care unit CAP were randomly assigned to receive either oral levofloxacin or sequential antibiotic treatment. Direct and indirect costs were compared over a 30-day period from several perspectives.

CAP resolved in 71 out of 77 oral levofloxacin (92%) and in 34 out of 37 sequential antibiotic treatment patients (92%). Patients' characteristics, treatment duration, hospital length of stay and mortality were similar in both groups. Drug acquisition costs were 1.7-times smaller in oral levofloxacin patients, who were less often transferred to rehabilitation centres, but they used more physicians' visits during follow-up and their total costs were lower. As only a minority of patients was still active, inability to work and, hence, indirect costs were similar in both groups.

In this study, oral levofloxacin for severe non-intensive care unit community-acquired pneumonia was equally effective as sequential antibiotic treatment, but did not lead to major costs savings except for drug acquisition costs. External factors linked with patients' characteristics and/or medical practice are likely to play a role and should be addressed.
Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture
Authors: Holz O. , Zühlke I. , Jaksztat E. , Müller K.C. , Welker L. , Nakashima M. , Diemel K.D. , Branscheid D. , Magnussen H. , Jörres R.A.
Published: September 2004

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema.

Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined.

In emphysema, mean±semDT was 33.6±2.8 h compared with 24.8±1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4–22.6)versus20.2 (11.2–25.5)).

The current authors, therefore, suggest that the reduced proliferation ratein vitroof lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.
Characterisation of post-pneumonectomy lung growth in adult mice
Authors: Voswinckel R. , Motejl V. , Fehrenbach A. , Wegmann M. , Mehling T. , Fehrenbach H. , Seeger W.
Published: September 2004

A model of inducible expansion of the gas exchange area in adult mice would be ideal for the investigation of molecular determinants of airspace regenerationin vivo. Therefore, the post-pneumonectomy (post-PNX) compensatory lung growth in adult C57BL/6 mice was characterised in this study.

Mice underwent left-sided PNX. Right lung volume was assessed on days 1, 3, 5, 7, 10 and 21 after PNX, and total DNA and cellular proliferation of the right lung were determined. Lung histology was studied using immunohistochemistry and quantitatively characterised by detailed stereological investigations. Pulmonary function was assessed using a mouse body-plethysmograph.

Following PNX, right-lung volume rapidly restored the initial volume of left and right lung. Total DNA increased significantly over 21 days and equalled the total DNA amount of both lungs in the control mice. Septal cell proliferation significantly increased after PNX, and included endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. Stereological investigations of left and right control lungsversusright lungs 21 days after PNX indicated complete restoration of body mass-specific alveolar surface area. Pulmonary function testing showed marked alteration at 3 days and normalisation at 21 days post-PNX.

In conclusion, well reproducible reconstitution of alveolar gas-exchange surface based on septal tissue expansion may be provoked by pneumonectomy in adult mice.
A combinational feature selection and ensemble neural network method for classification of gene expression data
Authors: Liu Bing , Cui Qinghua , Jiang Tianzi , Ma Songde
Published: September 2004

Background

Microarray experiments are becoming a powerful tool for clinical diagnosis, as they have the potential to discover gene expression patterns that are characteristic for a particular disease. To date, this problem has received most attention in the context of cancer research, especially in tumor classification. Various feature selection methods and classifier design strategies also have been generally used and compared. However, most published articles on tumor classification have applied a certain technique to a certain dataset, and recently several researchers compared these techniques based on several public datasets. But, it has been verified that differently selected features reflect different aspects of the dataset and some selected features can obtain better solutions on some certain problems. At the same time, faced with a large amount of microarray data with little knowledge, it is difficult to find the intrinsic characteristics using traditional methods. In this paper, we attempt to introduce a combinational feature selection method in conjunction with ensemble neural networks to generally improve the accuracy and robustness of sample classification.

Results

We validate our new method on several recent publicly available datasets both with predictive accuracy of testing samples and through cross validation. Compared with the best performance of other current methods, remarkably improved results can be obtained using our new strategy on a wide range of different datasets.

Conclusions

Thus, we conclude that our methods can obtain more information in microarray data to get more accurate classification and also can help to extract the latent marker genes of the diseases for better diagnosis and treatment.
A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects
Authors: Liu Shiliang , West Roy , Randell Edward , Longerich Linda , O'Connor Kathleen Steel , Scott Helen , Crowley Marian , Lam Angeline , Prabhakaran Victor , McCourt Catherine
Published: September 2004

Background

Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention.

Methods

This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements.

Results

The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%.

Conclusions

Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue.
Using email reminders to engage physicians in an Internet-based CME intervention
Authors: Abdolrasulnia Maziar , Collins Blanche C , Casebeer Linda , Wall Terry , Spettell Claire , Ray Midge N , Weissman Norman W , Allison Jeroan J
Published: September 2004

Background

Engaging practicing physicians in educational strategies that reinforce guideline adoption and improve the quality of healthcare may be difficult. Push technologies such as email offer new opportunities to engage physicians in online educational reinforcing strategies. The objectives are to investigate 1) the effectiveness of email announcements in engaging recruited community-based primary care physicians in an online guideline reinforcement strategy designed to promote Chlamydia screening, 2) the characteristics of physicians who respond to email announcements, as well as 3) how quickly and when they respond to email announcements.

Methods

Over a 45-week period, 445 recruited physicians received up to 33 email contacts announcing and reminding them of an online women's health guideline reinforcing CME activity. Participation was defined as physician log-on at least once to the website. Data were analyzed to determine participation, to compare characteristics of participants with recruited physicians who did not participate, and to determine at what point and when participants logged on.

Results

Of 445 recruited physicians with accurate email addresses, 47.2% logged on and completed at least one module. There were no significant differences by age, race, or specialty between participants and non-participants. Female physicians, US medical graduates and MDs had higher participation rates than male physicians, international medical graduates and DOs. Physicians with higher baseline screening rates were significantly more likely to log on to the course. The first 10 emails were the most effective in engaging community-based physicians to complete the intervention. Physicians were more likely to log on in the afternoon and evening and on Monday or Thursday.

Conclusions

Email course reminders may enhance recruitment of physicians to interventions designed to reinforce guideline adoption; physicians' response to email reminders may vary by gender, degree, and country of medical training. Repetition of email communications contributes to physician online participation.
Components of a modern mental health service: a pragmatic balance of community and hospital care
Authors: Thornicroft Graham , Tansella Michele
Published: September 2004

Background

There is controversy about whether mental health services should be provided in community or hospital settings. There is no worldwide consensus on which mental health service models are appropriate in low-, medium- and high-resource areas.

Aims

To provide an evidence base for this debate, and present a stepped care model.

Method

Cochrane systematic reviews and other reviews were summarised.

Results

The evidence supports a balanced approach, including both community and hospital services. Areas with low levels of resources may focus on improving primary care, with specialist back-up. Areas with medium resources may additionally provide out-patient clinics, community mental health teams (CMHTs), acute in-patient care, community residential care and forms of employment and occupation. High-resource areas may provide all the above, together with more specialised services such as specialised out-patient clinics and CMHTs, assertive community treatment teams, early intervention teams, alternatives to acute in-patient care, alternative types of community residential care and alternative occupation and rehabilitation.

Conclusions

Both community and hospital services are necessary in all areas regardless of their level of resources, according to the additive and sequential stepped care model described here.
Cognitive therapy for the prevention of psychosis in people at ultra-high risk
Authors: Morrison Anthony P. , French Paul , Walford Lara , Lewis Shôn W. , Kilcommons Aoiffe , Green Joanne , Parker Sophie , Bentall Richard P.
Published: September 2004

Background

Advances in the ability to identify people at high risk of developing psychosis have generated interest in the possibility of preventing psychosis.

Aims

To evaluate the efficacy of cognitive therapy for the prevention of transition to psychosis.

Method

A randomised controlled trial compared cognitive therapy with treatment as usual in 58 patients at ultra-high risk of developing a first episode of psychosis. Therapy was provided over 6 months, and all patients were monitored on a monthly basis for 12 months.

Results

Logistic regression demonstrated that cognitive therapy significantly reduced the likelihood of making progression to psychosis as defined on the Positive and Negative Syndrome Scale over 12 months. In addition, it significantly reduced the likelihood of being prescribed antipsychotic medication and of meeting criteria for a DSM – IV diagnosis of a psychotic disorder. Analysis of covariance showed that the intervention also significantly improved positive symptoms of psychosis in this population over the 12-month period.

Conclusions

Cognitive therapy appears to be an acceptable and efficacious intervention for people at high risk of developing psychosis.
Prevalence and correlates of self-reported psychotic symptoms in the British population
Authors: Johns Louise C. , Cannon Mary , Singleton Nicola , Murray Robin M. , Farrell Michael , Brugha Traolach , Bebbington Paul , Jenkins Rachel , Meltzer Howard
Published: September 2004

Background

The psychosis phenotype is generally thought of as a categorical entity. However, there is increasing evidence that psychosis exists in the population as a continuum of severity rather than an all-or-none phenomenon.

Aims

To investigate the prevalence and correlates of self-reported psychotic symptoms using data from the 2000 British National Survey of Psychiatric Morbidity.

Method

A total of 8580 respondents aged 16–74 years were interviewed. Questions covered mental health, physical health, substance use, life events and socio-demographic variables. The Psychosis Screening Questionnaire (PSQ) was used to identify psychotic symptoms.

Results

Of the respondents, 5.5% endorsed one or more items on the PSQ. Factors independently associated with psychotic symptoms were cannabis dependence, alcohol dependence, victimisation, recent stressful life events, lower intellectual ability and neurotic symptoms. Male gender was associated with paranoid thoughts, whereas female gender predicted hallucinatory experiences.

Conclusions

Self-reported psychotic symptoms are less common in this study than reported elsewhere, because of the measure used. These symptoms have demographic and clinical correlates similar to clinical psychosis.
Characteristics of teams, staff and patients: associations with outcomes of patients in assertive outreach
Authors: Priebe Stefan , Fakhoury Walid , White Ian , Watts Joanna , Bebbington Paul , Billings Joanna , Burns Tom , Johnson Sonia , Muijen Matt , Ryrie Iain , Wright Christine
Published: September 2004

Background

Little is known about what characteristics of teams, staff and patients are associated with a favourable outcome of severe mental illness managed by assertive outreach.

Aims

To identify predictors of voluntary and compulsory admissions in routine assertive outreach services in the UK.

Method

Nine features of team organisation and policy, five variables assessing staff satisfaction and burn-out and eleven patient characteristics taken from the baseline data of the Pan-London Assertive Outreach Study were tested as predictors of voluntary and compulsory admissions within a 9-month follow-up period.

Results

Weekend working, staff burn-out and lack of contact of the patient with other services were associated independently with a higher probability of both voluntary and compulsory admission. In addition, admissions in the past predicted further voluntary and compulsory admissions, and teams not working extended hours predicted compulsory admissions in the follow-up period.

Conclusions

Characteristics of team working practice, staff burn-out and patients' history are associated independently with outcome. Patient contact with other services is a positive prognostic factor.
In hospital, at home, or not at all
Authors: Crawford Mike J. , Gibbon Rebecca , Ellis Elizabeth , Waters Hannah
Published: September 2004

Aims and Method

In view of plans to reform Mental Health Act legislation to allow compulsory treatment in the community, we examined the views of service users about this form of care, and the most acceptable setting for its delivery. A cross-sectional survey of patients discharged from two in-patient units in West London over a 5-month period was carried out.

Results

Half of the 109 respondents stated that compulsory treatment was justified under some circumstances; 103 people told us where they would prefer to receive compulsory treatment – 49 in their home, 41 in hospital and 13 in a community treatment centre. The most commonly stated reason for favouring home treatment was dislike of in-patient care.

Clinical Implications

Compulsory treatment in the community may provide a means of improving patient experiences of non-consensual care. However, a significant minority of service users would rather this form of treatment was restricted to in-patient units. Continuing efforts are required to improve patient experiences of in-patient care.
Phase I Trial of Intrathecal Liposomal Cytarabine in Children With Neoplastic Meningitis
Authors: Bomgaars L. , Geyer J.R. , Franklin J. , Dahl G. , Park J. , Winick N.J. , Klenke R. , Berg S.L. , Blaney S.M.
Published: September 2004

Purpose

We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children ≥ 3 years of age with advanced meningeal malignancies.

Patients and Methods

Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients.

Results

Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response.

Conclusion

The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.
Inpatient Versus Outpatient Management of Low-Risk Pediatric Febrile Neutropenia: Measuring Parents' and Healthcare Professionals' Preferences
Authors: Sung Lillian , Feldman Brian M. , Schwamborn Gina , Paczesny Diana , Cochrane Ashley , Greenberg Mark L. , Maloney Anne Marie , Hendershot Eleanor I. , Naqvi Ahmed , Barrera Maru , Llewellyn-Thomas Hilary A.
Published: September 2004

Purpose

Our primary objective was to describe and compare parents' and healthcare professionals' strength of preference scores for outpatient oral antibiotic relative to inpatient parenteral antibiotic treatment for low-risk febrile neutropenic children. Our secondary objective was to identify predictors of strength of preference for oral outpatient treatment.

Methods

Respondents were parents of children receiving cancer chemotherapy, and pediatric oncology healthcare professionals. First, the inpatient and outpatient options were described, and the respondent indicated their initially preferred option. The respondent next ranked how important seven factors (including “fear/anxiety” and “comfort”) were in making their initial choice. The threshold technique was then used to elicit the respondent's strength of preference score for oral outpatient, relative to parenteral inpatient management.

Results

There were 75 parent and 42 healthcare-professional respondents. There was no significant difference (P = .08) in the proportions of parents (40 of 75; 53%) and healthcare professionals (30 of 42; 71%) who initially would choose outpatient management. For parents, stronger preference for oral outpatient therapy was associated with higher anticipated quality of life for the parent and child at home relative to hospital, lower importance rank for “fear/anxiety,” and higher importance rank for “comfort.” Conversely, for professionals, only lower importance rank for “fear/anxiety” was associated with higher strength of preference scores for outpatient oral antibiotic management.

Conclusion

Only 53% of parents would choose outpatient oral antibiotic management for low-risk febrile neutropenia. Predictors of strength of preference scores for outpatient oral antibiotic relative to inpatient parenteral antibiotic treatment differed between parent and professional respondents.
Serial Follow-Up and the Prognostic Significance of Reverse Transcriptase-Polymerase Chain Reaction—Staged Sentinel Lymph Nodes From Melanoma Patients
Authors: Kammula Udai S. , Ghossein Ronald , Bhattacharya Satyajit , Coit Daniel G.
Published: September 2004

Purpose

Reverse transcriptase-polymerase chain reaction (RT-PCR) may provide an extremely sensitive method for detection of occult nodal disease. We evaluated the role of a single-marker RT-PCR assay for tyrosinase mRNA in the detection of melanoma sentinel lymph node (SLN) metastases and correlated the results with long-term clinical outcome.

Patients and Methods

One hundred twelve patients who underwent SLN biopsy for melanoma were prospectively analyzed. SLNs were bivalved, with half of each specimen evaluated by histologic methods and the other half evaluated by nested RT-PCR for tyrosinase.

Results

Fifteen patients (13%) had histologically positive SLNs, all of whom were also positive by RT-PCR (HISTO+/PCR+). Thirty-nine patients (35%) had SLNs that were negative by both histology and RT-PCR (HISTO−/PCR−). Fifty-eight patients (52%) were histologically negative but upstaged with a positive RT-PCR result (HISTO−/PCR+). Initially, at a median follow-up of 42 months, recurrence rates among the three cohorts were statistically different (HISTO+/PCR+, 53%; HISTO−/PCR+, 14%; and HISTO−/PCR−, 0%). However, at a longer median follow-up (67 months), recurrence rates for the HISTO−/PCR+ (24%) and HISTO−/PCR− (15%) groups were no longer statistically different (P = .25). The median time to relapse between the HISTO−/PCR+ and HISTO−/PCR− groups differed by 10 months (31 v 41 months, respectively).

Conclusion

With extended follow-up of patients with histologically negative SLNs, detection of submicroscopic disease by tyrosinase RT-PCR does not define a subgroup that is at higher recurrence risk when compared with patients with RT-PCR–negative SLNs. Future studies evaluating molecular staging will require approximately 5 years of median follow-up to accurately define outcome for patients with occult melanoma metastases.
Breast Cancer Treatment in Older Women: Does Getting What You Want Improve Your Long-Term Body Image and Mental Health?
Authors: Figueiredo Melissa I. , Cullen Jennifer , Hwang Yi-Ting , Rowland Julia H. , Mandelblatt Jeanne S.
Published: September 2004

Purpose

Little is known about the impact of surgical treatment on body image and health outcomes in older breast cancer patients. The purpose of this article is to evaluate whether concordance between treatment received and treatment preferences predicts posttreatment body image and whether body image, in turn, affects mental health in older women with breast cancer 2 years after treatment.

Patients and Methods

A longitudinal cohort of 563 women who were 67 years old or older and who had stages I and II breast cancer were surveyed by telephone at 3, 12, and 24 months after surgery. All women were clinically eligible for breast conservation. Body image was measured using questions adapted from the Cancer Rehabilitation Evaluation System–Short Form, and mental health was evaluated using a Medical Outcomes Study subscale.

Results

Body image was an important factor in treatment decisions for 31% of women. Women who received breast conservation had better body image 2 years after treatment than women who had mastectomies (P < .0001). Women who preferred breast conservation but received mastectomy had the poorest body image. Using generalized estimating equations, we found that body image, in turn, predicted 2-year mental health.

Conclusion

Body image is important for many older women, and receiving treatment consistent with preferences about appearance was important in long-term mental health outcomes. Health professionals should elicit preferences about appearance from women and provide treatment choices in concordance with these preferences. Enhancing shared decision making has the potential to improve mental health in older breast cancer survivors.
Phase III Double-Blind Placebo-Controlled Study of Farnesyl Transferase Inhibitor R115777 in Patients With Refractory Advanced Colorectal Cancer
Authors: Rao S. , Cunningham D. , de Gramont A. , Scheithauer W. , Smakal M. , Humblet Y. , Kourteva G. , Iveson T. , Andre T. , Dostalova J. , Illes A. , Belly R. , Perez-Ruixo J.J. , Park Y.C. , Palmer P.A.
Published: September 2004

Purpose

To determine whether R115777 improves survival in patients with refractory advanced colorectal cancer (CRC) in a multicenter, double-blind, prospective randomized study.

Patients and Methods

Three hundred sixty-eight patients were randomly assigned to R115777 (300 mg twice daily) orally for 21 days every 28 days or placebo in a 2:1 ratio. All patients received best supportive care. The primary end point was overall survival; secondary end points were progression free survival, tumor response, toxicity, and quality of life.

Results

The two treatment groups were well balanced for baseline demographics, including previous chemotherapy for advanced CRC. The median overall survival for R115777 was 174 days (95% CI, 157 to 198 days), and 185 days (95% CI, 158 to 238 days) for those patients receiving placebo (P = .376). One patient achieved a partial response in the R115777 arm. Stable disease (> 3 months) was observed in 24.3% patients in the R115777 group compared to 12.8% in the placebo arm. This did not translate into a statistically significant increase in progression-free survival. Overall, treatment was well tolerated. There was an increased incidence of reversible myelosuppression (neutropenia, thrombocytopenia), rash, and grade 1 to 2 diarrhea in the R115777 arm. There was no statistically significant difference in quality of life between arms.

Conclusion

Single agent R115777 , given at this dose and schedule, has an acceptable toxicity profile, but does not improve overall survival compared to best supportive care alone in refractory advanced CRC.
Association Between Aryl Hydrocarbon Receptor Genotype and Survival in Soft Tissue Sarcoma
Authors: Berwick Marianne , Matullo Giuseppe , Song Yan Shuang , Guarrera Simonetta , Dominguez Gemma , Orlow Irene , Walker Mary , Vineis Paolo
Published: September 2004

Purpose

Accumulating evidence shows that germline polymorphisms may affect survival in cancer. The purpose of this study was to investigate the association between polymorphisms in a group of candidate genes and survival with soft tissue sarcoma.

Patients and Methods

We measured single nucleotide polymorphisms in the metabolizing, detoxifying, and DNA repair pathways in 120 newly diagnosed patients with soft tissue sarcoma. We assessed polymorphisms in the aryl hydrocarbon receptor (AhR-Arg554Lys), null variants of the glutathione S-transferase superfamily (GSTM1 and GSTT1), x-ray repair cross-complementing 1 and 3, and Xeroderma pigmentosum, group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln). We followed the patients for survival for a median of 7.6 years.

Results

Cox proportional hazards models demonstrated that a polymorphism at codon 554 in exon 10 of the AhR was significantly and adversely associated with survival (hazard ratio, 2.2; 95% CI, 1.3 to 3.9; P < .01), even while accounting for major clinical characteristics such as tumor grade, tumor size, anatomic site, and patient age.

Conclusion

Further study of the role of the AhR polymorphism is warranted.
Testis-specific TAF homologs collaborate to control a tissue-specific transcription program
Authors: Hiller Mark , Chen Xin , Pringle M. Jodeane , Suchorolski Martin , Sancak Yasemin , Viswanathan Sridhar , Bolival Benjamin , Lin Ting-Yi , Marino Susan , Fuller Margaret T.
Published: September 2004

Alternate forms of the PolII transcription initiation machinery have been proposed to play a role in selective activation of cell-type-specific gene expression programs during cellular differentiation. The cannonball(can) gene of Drosophila encodes a homolog of a TBP-associated factor (dTAF5) protein expressed only in spermatocytes, where it is required for normal transcription of genes required for spermatid differentiation. We show that Drosophila primary spermatocytes also express four additional tissue-specific TAFs: nht (homolog of dTAF4), mia (homolog of dTAF6), sa (homolog of dTAF8) and rye (homolog of dTAF12). Mutations in nht, mia and sa have similar effects in primary spermatocytes on transcription of several target genes involved in spermatid differentiation, and cause the same phenotypes as mutations in can, blocking both meiotic cell cycle progression and spermatid differentiation. The nht, mia, sa and rye proteins contain histone fold domain dimerization motifs. The nht and rye proteins interact structurally when co-expressed in bacteria, similarly to their generally expressed homologs TAF4 and TAF12,which heterodimerize. Strikingly, the structural interaction is tissue specific: nht did not interact with dTAF12 and dTAF4 did not interact with rye in a bacterial co-expression assay. We propose that the products of the five Drosophila genes encoding testis TAF homologs collaborate in an alternative TAF-containing protein complex to regulate a testis-specific gene expression program in primary spermatocytes required for terminal differentiation of male germ cells.
Pax8 and Pax2a function synergistically in otic specification, downstream of the Foxi1 and Dlx3b transcription factors
Authors: Hans Stefan , Liu Dong , Westerfield Monte
Published: September 2004

The vertebrate inner ear arises from an ectodermal thickening, the otic placode, that forms adjacent to the presumptive hindbrain. Previous studies have suggested that competent ectodermal cells respond to Fgf signals from adjacent tissues and express two highly related paired box transcription factors Pax2a and Pax8 in the developing placode. We show that compromising the functions of both Pax2a and Pax8 together blocks zebrafish ear development, leaving only a few residual otic cells. This suggests that Pax2a and Pax8 are the main effectors downstream of Fgf signals. Our results further provide evidence that pax8 expression and pax2a expression are regulated by two independent factors, Foxi1 and Dlx3b, respectively. Combined loss of both factors eliminates all indications of otic specification. We suggest that the Foxi1-Pax8 pathway provides an early`jumpstart' of otic specification that is maintained by the Dlx3b-Pax2a pathway.
Developmental architecture of adult-specific lineages in the ventral CNS ofDrosophila
Authors: Truman James W. , Schuppe Hansjürgen , Shepherd David , Williams Darren W.
Published: September 2004

In Drosophila most thoracic neuroblasts have two neurogenic periods: an initial brief period during embryogenesis and a second prolonged phase during larval growth. This study focuses on the adult-specific neurons that are born primarily during the second phase of neurogenesis. The fasciculated neurites arising from each cluster of adult-specific neurons express the cell-adhesion protein Neurotactin and they make a complex scaffold of neurite bundles within the thoracic neuropils. Using MARCM clones, we identified the 24 lineages that make up the scaffold of a thoracic hemineuromere. Unlike the early-born neurons that are strikingly diverse in both form and function, the adult specific cells in a given lineage are remarkably similar and typically project to only one or two initial targets,which appear to be the bundled neurites from other lineages. Correlated changes in the contacts between the lineages in different segments suggest that these initial contacts have functional significance in terms of future synaptic partners. This paper provides an overall view of the initial connections that eventually lead to the complex connectivity of the bulk of the thoracic neurons.
Drosophila contactin, a homolog of vertebrate contactin, is required for septate junction organization and paracellular barrier function
Authors: Faivre-Sarrailh Catherine , Banerjee Swati , Li Jingjun , Hortsch Michael , Laval Monique , Bhat Manzoor A.
Published: September 2004

Septate junctions (SJs) in epithelial and neuronal cells play an important role in the formation and maintenance of charge and size selective barriers. They form the basis for the ensheathment of nerve fibers in Drosophila and for the attachment of myelin loops to axonal surface in vertebrates. The cell-adhesion molecules NRX IV/Caspr/Paranodin (NCP1),contactin and Neurofascin-155 (NF-155) are all present at the vertebrate axo-glial SJs. Mutational analyses have shown that vertebrate NCP1 and its Drosophila homolog, Neurexin IV (NRX IV) are required for the formation of SJs. In this study, we report the genetic, molecular and biochemical characterization of the Drosophila homolog of vertebrate contactin, CONT. Ultrastructural and dye-exclusion analyses of Contmutant embryos show that CONT is required for organization of SJs and paracellular barrier function. We show that CONT, Neuroglian (NRG)(Drosophila homolog of NF-155) and NRX IV are interdependent for their SJ localization and these proteins form a tripartite complex. Hence, our data provide evidence that the organization of SJs is dependent on the interactions between these highly conserved cell-adhesion molecules.
How different is Venus from Mars? The genetics of germ-line stem cells inDrosophilafemales and males
Authors: Gilboa Lilach , Lehmann Ruth
Published: September 2004

In the fruit fly Drosophila melanogaster, both spermatogenesis and oogenesis rely on germ-line stem cells (GSCs). Intensive research has revealed many of the molecules and pathways that underlie GSC maintenance and differentiation in males and females. In this review, we discuss new studies that, some differences notwithstanding, highlight the similarities in the structural and molecular strategies used by the two sexes in GSC maintenance and differentiation. These include the tight control that somatic support cells exert on every aspect of GSC function and the similar molecular mechanisms for physical attachment, cell-cell signaling and gap-junction communication. Some common principles underlying GSC biology in the fly may be applied to stem cells in other organisms.
Citron Kinase is an essential effector of the Pbl-activated Rho signalling pathway inDrosophila melanogaster
Authors: Shandala Tetyana , Gregory Stephen L. , Dalton Hazel E. , Smallhorn Masha , Saint Robert
Published: September 2004

Pebble (Pbl)-activated RhoA signalling is essential for cytokinesis in Drosophila melanogaster. Here we report that the Drosophila citron gene encodes an essential effector kinase of Pbl-RhoA signalling in vivo. Drosophila citron is expressed in proliferating tissues but is downregulated in differentiating tissues. We find that Citron can bind RhoA and that localisation of Citron to the contractile ring is dependent on the cytokinesis-specific Pbl-RhoA signalling. Phenotypic analysis of mutants showed that citron is required for cytokinesis in every tissue examined, with mutant cells exhibiting multinucleate and hyperploid phenotypes. Strong genetic interactions were observed between citronand pbl alleles and constructs. Vertebrate studies implicate at least two Rho effector kinases, Citron and Rok, in cytokinesis. By contrast, we failed to find evidence for a role for the Drosophila ortholog of Rok in cell division. We conclude that Citron plays an essential, non-redundant role in the Rho signalling pathway during Drosophila cytokinesis.