bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory cell mapping of the respiratory tract in fatal asthma
Authors: De Magalhães Simões S. , Dos Santos M. A. , Da Silva Oliveira M. , Fontes E. S. , Fernezlian S. , Garippo A. L. , Castro I. , Castro F. F. M. , De Arruda Martins M. , Saldiva P. H. N. , Mauad T. , Dolhnikoff M. 
Published: May 2005

SummaryBackground
The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways.Objective
We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma.Methods
Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls.Results
Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028).Conclusion
Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA.
Increase in killer‐specific secretory protein of 37 kDa in bronchoalveolar lavage fluid of allergen‐challenged patients with atopic asthma
Authors: Kuepper M. , Bratke K. , Julius P. , Ogawa K. , Nagata K. , Luttmann W. , Virchow J. C. 
Published: May 2005

SummaryBackground
Atopic asthma is linked to a T‐helper type 2 dominated pathogenesis, but there is increasing evidence of Th1/Tc1‐mediated processes in the aetiopathology of asthma. Killer‐specific secretory protein of 37 kDa (Ksp37) is expressed in cytotoxic lymphocytes, selectively in the effector subsets of CD8+‐ and CD4+ T lymphocytes and in CD16+/CD56dim natural killer cells and γ/δ T cells. This effector cell‐specific expression of Ksp37 and its coexpression with perforin suggest that Ksp37 might be involved in processes mediated by cytotoxic cells.Objective
We hypothesize that Ksp37 could indicate the involvement of cytotoxic lymphocytes in the pathogenesis of atopic asthma, and investigated Ksp37 concentration in bronchoalveolar lavage fluid (BALF) collected 10 min, 18, 42 or 162 h after segmental allergen provocation and in serum of patients with atopic asthma (n=25).Methods
Ksp37 concentrations in BALF and serum were detected by ELISA. Flow cytometric analysis was used to assess numbers and cell subsets in BALF.Results
Ksp37 increased significantly in BALF 10 min, 18 and 42 h, but not 162 h after allergen challenge compared with saline‐challenged controls, while Ksp37 serum levels did not change significantly at all time‐points. In addition, the increase in Ksp37 concentrations in BALF correlated with the corresponding numbers of lymphocytes.Conclusions
We conclude that Ksp37 level increased in BALF 10 min, 18 and 42 h after allergen challenge but not in peripheral blood. Our findings suggest that segmental allergen challenge in asthma is associated with an increase in Ksp37 concentrations in BALF and an influx of potentially cytotoxic T lymphocytes into the lungs.
Effects of calcineurin inhibitors on an in vitro assay for chronic urticaria
Authors: Marsland A. M. , Soundararajan S. , Joseph K. , Kaplan A. P. 
Published: May 2005

SummaryBackground
Chronic urticaria is a common skin disorder, which causes considerable morbidity. In approximately 40% of cases, patients have an autoimmune disorder in which functional antibodies cause degranulation of mast cells and basophils, and C5a complement augments this in varying amounts from patient to patient. Since the calcineurin inhibitor ciclosporin has been used in chronic autoimmune urticaria, we examined the effect of ciclosporin and other drugs on the release of histamine from basophils when stimulated by sera from patients with chronic autoimmune urticaria.Methods
Leucocytes from healthy donors were isolated and incubated in varying concentrations of ciclosporin, ascomycin, methotrexate, diphenhydramine or hydroxyzine for 30 min prior to stimulation with serum from urticaria patients known to have functional immunoglobulin (Ig)G antibodies directed against the alpha subunit of the IgE receptor. Histamine release was then measured.Results
Pre‐incubating cells with ciclosporin and ascomycin produced dose‐dependent inhibition of histamine release when cells were stimulated by sera of urticaria patients, by purified IgG from these sera, but not by C5a. Inhibition was not prevented by C5a receptor blocking antibodies. No inhibition was seen with methotrexate, diphenhydramine or hydroxyzine.Conclusions
This is the first demonstration of inhibition of histamine release by calcineurin inhibitors employing sera of patients with chronic autoimmune urticaria. These drugs may work by interfering with intracellular signalling in cells following cross‐linking of the IgE receptor, but not following stimulation of the C5a receptor.
Low socioeconomic status as a risk factor for asthma, rhinitis and sensitization at 4 years in a birth cohort
Authors: Almqvist C. , Pershagen G. , Wickman M. 
Published: May 2005

SummaryBackground
The relation between socioeconomic status and allergic diseases in childhood is controversial. Some studies have proposed childhood asthma to be more common in families with low socioeconomic status, while sensitization to airborne allergens seems to be more frequent in individuals with higher socioeconomic status in childhood.Objective
To assess the relation between socioeconomic status and asthma, rhinitis and sensitization in an unselected prospective birth cohort.Methods
Four thousand and eighty‐nine families with children born 1994–1996 in predefined areas of Stockholm answered questionnaires on environmental factors, socioeconomic status (parental occupation), and symptoms of allergic disease at birth, 1, 2 and 4 years of age. Blood samples taken at 4 years from 2614 children were analysed for specific IgE to common airborne and food allergens. Odds ratios (OR) and 95% confidence intervals (CI) for various outcomes in relation to socioeconomic status were estimated with a multiple logistic regression model, adjusting for potential confounders such as heredity for allergic diseases, maternal smoking, short duration of breastfeeding and house construction.Results
There was a decreasing risk of asthma and rhinitis with increasing socioeconomic status. The OR for asthma was 0.33 (95% CI 0.17–0.66) and for rhinitis 0.50 (0.32–0.79) comparing the highest and the lowest socioeconomic groups, with a tendency to stronger effects in those with heredity for allergic disease. The risk of sensitization to food allergens also decreased with increasing socioeconomic status; OR 0.65 (0.41–1.02) in the highest socioeconomic group (Ptrend=0.03), which was not clearly seen for airborne allergens.Conclusion
Asthma, rhinitis and sensitization is more common in lower than in higher socioeconomic groups after adjustment for traditional risk factors. This may be related to additional uncontrolled differences in life style and environmental exposures between the groups, and calls for further studies.
Methotrexate therapy of oral corticosteroid‐dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy
Authors: Corrigan C. J. , Shiner R. J. , Shakur B. H. , Ind P. W. 
Published: May 2005

SummaryBackground
Concomitant methotrexate (MTX) therapy of oral corticosteroid (CS)–dependent asthmatics has been shown to spare CS therapy, but the mechanism is unknown. In a previous report, we showed that MTX increases T cell inhibition by CS. In this report we focus on effects of MTX on immunoglobulin concentrations and their possible clinical relevance.Objective
To monitor changes in circulating leucocytes and Ig in a group of these patients during MTX therapy, and to relate these changes to clinical ‘response’ as defined by oral CS reduction.Methods
Sixteen severe asthmatics dependent on oral prednisolone 15 (7.5–25) mg/day in addition to high dose inhaled CS were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. Prednisolone dosages were maintained constant for 12 weeks then reduced systematically over the next 16 weeks provided that asthma control did not deteriorate. Patients were classified a priori as ‘responders’ or ‘non‐responders’ to MTX (reduction of initial oral prednisolone requirement by 50% or <50%, respectively). Patients were followed‐up for a further 12 weeks after MTX withdrawal. Serum Ig and differential blood leucocyte counts were measured at baseline, 12, 28 and 40 weeks.Results
MTX therapy allowed significant, but individually variable, reductions in oral prednisolone dosages (P<0.00001) without alteration of lung function or symptoms. This was associated with significant reductions in mean serum concentrations of Ig of all classes, which reversed following MTX withdrawal. Reductions in IgE and IgG were significantly greater in the MTX ‘responders’ as compared with ‘non‐responders’, and changes in IgE, IgG and IgM correlated with changes in prednisolone requirements. Differential blood leucocyte counts showed no significant variation.Conclusion
MTX therapy reduced oral CS requirements in these severe asthmatics to a degree which correlated with reduced circulating Ig but not lymphopaenia, suggesting a possible cause and effect relationship. These reductions might also contribute to the documented incidence of opportunistic infection in these circumstances.
Growing pains: Non‐adherence with the immunosuppressive regimen in adolescent transplant recipients
Authors: Dobbels Fabienne , Damme‐Lombaert Rita Van , Vanhaecke Johan , Geest Sabina De 
Published: May 2005

Abstract:  One‐year graft and patient survival are better in adolescent transplant recipients (age 11–19 years) than in younger (age < 11 years) pediatric transplant recipients. However, several groups found that long‐term outcomes (> i.e. 5 year post‐transplant) in the adolescent age group are significantly worse than in younger transplant recipients.A behavioral factor that could explain an important part of the poorer clinical outcome in adolescent transplant recipients is non‐compliance with medication taking. Adolescents, like all organ transplant recipients irrespective of their age, must adhere to a life‐long immunosuppressive regimen in addition to other aspects of their therapeutic regimen. Therefore, adolescent transplant recipients, as all transplant patients, should be regarded as a chronically ill patient population in whom behavioral and psychosocial management is equally important as state‐of‐the‐art medical management.This paper provides an overview of the current knowledge on prevalence, clinical consequences, and risk‐factors for non‐compliance with the immunosuppressive regimen in adolescent transplant recipients and offers some suggestions for adolescent‐tailored interventions to improve medication adherence.
Clinical correlates of current level of functioning in primary care‐treated bipolar patients
Authors: Hajek Tomas , Slaney Claire , Garnham Julie , Ruzickova Martina , Passmore Michael , Alda Martin 
Published: May 2005

Objectives:  In this study we examined general assessment of functioning (GAF), and its relation to clinical and demographic factors in bipolar patients. A number of studies, mostly from specialized programs, show that bipolar disorder often leads to occupational and social impairment. Here we report data from patients in a primary care setting.Methods:  A total of 252 patients from the Maritime Bipolar Registry with DSM‐IV diagnoses of bipolar I or bipolar II disorder participated in the study. GAF ratings during maintenance treatment were compared across clinical and demographic variables.Results:  The mean GAF score in this sample was 67 ± 17 (range 10–100). The GAF scores followed bimodal distribution with mean values of 50.5 ± 10.3 and 79.0 ± 10.3. Decreased functioning was found in patients with chronic illness course, history of rapid cycling, suicidal behaviour, psychiatric comorbidity, hypothyroidism, and diabetes mellitus, regardless of treatment of these conditions. There were no differences in the level of functioning between men and women, bipolar I and II patients, those with and without psychotic episodes, hypertension, treatment with antidepressants or antipsychotics.Conclusions:  Functioning in primary care‐treated bipolar patients in maintenance phase of treatment is decreased not only due to specific disorder‐related variables, but also due to frequent comorbidity with other psychiatric and medical conditions.
Pharmacotherapy of bipolar mixed states
Authors: Krüger Stephanie , Trevor Young L , Bräunig Peter 
Published: May 2005

Objective:  Mixed episodes comprise up to 40% of acute bipolar admissions. They are difficult‐to‐treat, complex clinical pictures. This review provides an overview of the available literature on the pharmacotherapy of manic‐depressive mixed states and suggests treatment options.Method:  Literature was identified by searches in Medline, Embase and the Cochrane Controlled Trials Register. Studies were considered relevant if they contained the keywords mixed mania, mixed state(s), mixed episode(s), treatment, therapy, study or trial.Results:  Overall, there were very few double‐blind, placebo‐controlled studies specifically designed to treat manic‐depressive mixed states. Rather, patients with mixed states comprised a sub‐group of the examined patient cohorts. Nevertheless, the data show that acute mixed states do not respond favourably to lithium. Instead, valproate and olanzapine are drugs of first choice. Carbamazepine may play a role in the prevention of mixed states. Antidepressants should be avoided, because they may worsen intraepisodic mood lability. Lamotrigine may be useful in treating mixed states with predominantly depressive symptoms.Conclusions:  More treatment studies specifically designed to treat the complex clinical picture of mixed states are clearly needed. Current treatment recommendations for clinical practice based on the available literature can only target select aspects of these episodes.
Gabapentin withdrawal syndrome in the presence of a taper
Authors: Tran Kien T , Hranicky Diane , Lark Tracey , Jacob NJ 
Published: May 2005

Objective:  To report a case report of a geriatric patient with a 5‐year history of gabapentin use for enhanced bipolar control, who was tapered off of gabapentin over 1 week. The patient displayed unique withdrawal symptoms after the taper of gabapentin.Methods:  The patient is an 81‐year‐old white female with a life‐long history of schizoaffective disorder with bipolar type I tendencies who had been prescribed gabapentin for 5 years.Results:  The patient displayed moderate upper respiratory tract infection symptoms and somatic complaints 1 day after termination of gabapentin. These symptoms gradually worsened until 10 days after, at which time she acutely developed severe mental status changes, severe somatic chest pain, and hypertension. Physical examination, electrolytes, electrocardiogram, computerized tomography, magnetic resonance imaging, and magnetic resonance angiography were all normal. Upon reintroduction of gabapentin, the patient returned to baseline within 1–2 days.Conclusions:  Gabapentin is widely utilized currently for the chronic treatment of recalcitrant migraines, bipolar illness, pain, and epilepsy. It has a wide therapeutic index with few side effects and drug interactions, is not hepatically metabolized, and is excreted by the kidneys. Past reports have suggested that some withdrawal symptoms can present after 1–2 days upon abrupt discontinuation of gabapentin after chronic use within young to middle‐aged patients. These symptoms mimic that of alcohol and benzodiazepine withdrawal purportedly due to a similar mechanism of action. Unique to this case is that this geriatric patient developed debilitating withdrawal symptoms after a gradual, week‐long taper of gabapentin along with flu‐like symptoms. It is proposed herein that a gabapentin taper should follow a course similar to that of a benzodiazepine taper – slowly and over a period of weeks to months.
Divalproex sodium for pediatric mixed mania: a 6‐month prospective trial
Authors: Pavuluri Mani N , Henry David B , Carbray Julie A , Naylor Michael W , Janicak Philip G 
Published: May 2005

Objective:  This prospective 6‐month open trial examined the effectiveness and safety of divalproex sodium (DVPX) in pediatric mixed mania.Method:  Thirty‐four subjects with a mean age of 12.3 (SD = 3.7) years, DSM‐IV diagnosis of a current mixed episode and a baseline Young Mania Rating Scale (YMRS) score >20 were treated with DVPX monotherapy. The primary outcome measures were the YMRS and the Child Depression Rating Scale‐Revised. Secondary measures were the Clinical Global Impression Scale for Bipolar Disorder (CGI‐BP) and the Children's Global Assessment of Functioning Scale (C‐GAS). Measures of safety and tolerability were also administered.Results:  Effect size (Cohen's d) based on change scores from baseline was 2.9 for the YMRS and 1.23 for the CDRS‐R. Response rate (≥50% change from baseline YMRS score and ≤40 score on CDRS‐R at the end of study) was 73.5%. The remission rate (≥50% change from baseline on YMRS, ≤40 on CDRS‐R, CGI‐BP‐Improvement subscale of ≤2, and ≥51 CGAS score) was 52.9%. Significant improvements (p < 0.001) from baseline were seen for mean scores on all outcome measures (i.e., YMRS, CGI‐BP, CDRS‐R, and C‐GAS). DVPX was safe and well tolerated with no serious adverse events during the 6‐month trial.Conclusion:  This study provides evidence for the effectiveness and safety of DVPX in the treatment of pediatric mixed mania over a 6‐month period. Placebo‐controlled, randomized trials involving larger samples will ultimately shed light on the efficacy of this agent.
Functional impairment in the remission phase of bipolar disorder
Authors: Fagiolini Andrea , Kupfer David J , Masalehdan Azadeh , Scott John A , Houck Patricia R , Frank Ellen 
Published: May 2005

Objectives:  The purpose of this study was to evaluate functional impairment in a group of patients with bipolar disorder in remission and to determine the extent of relationships between overall functioning and current depressive, manic and panic spectrum symptoms.Method:  A subset of the patient population at the Pittsburgh site of the Systematic Treatment Enhancement Program in Bipolar Disorder (STEP‐BD) study was evaluated in this study. The subsample comprises 103 male and female subjects with bipolar I disorder (n = 70), bipolar II disorder (n = 24), schizoaffective disorder – bipolar type (n = 4), or bipolar disorder NOS (n = 5). Subjects were evaluated in a period of remission (at least 4 weeks with no more than two depressive or manic symptoms). Subjects were assessed for overall functional status using the Work and Social Adjustment Scale (WSAS) and for current bipolar and panic spectrum symptoms using the Mood Spectrum Self‐Report questionnaire (MOODS‐SR) and Panic‐Agoraphobic Spectrum Self‐Report questionnaire (PAS‐SR).Results:  The median WSAS total score in these remitted subjects was 14, indicating significant functional impairment. Regressing WSAS on current depressive, manic, and panic spectrum total scores, we observed a highly significant depressive spectrum effect (t = 4.9, df = 94, p < 0.0001), but non‐significant panic and manic spectrum effects (t = 1.3, df = 94, p = 0.19 and t = −1.8, df = 94, p = 0.07, respectively).Conclusion:  Bipolar disorder is associated with functional deficits even during periods of sustained and substantial remission. The degree of functional impairment is correlated with the degree of depressive spectrum symptoms.
PREOPERATIVE CHEMOTHERAPY AND RADIOTHERAPY FOR LOCALLY ADVANCED RECTAL CANCER
Authors: Chao Michael , Gibbs Peter , Tjandra Joe , Cullinan Mark , McLaughlin Stephen , Faragher Ian , Skinner Iain , Jones Ian 
Published: May 2005

Background:  The adjuvant treatment of rectal cancer is a rapidly evolving field. The standard approach is a combination of chemotherapy and radiotherapy, with the optimal treatment combination and sequencing yet to be determined. Here, we report our early experience of preoperative chemotherapy and radiotherapy (CRT) in locally advanced rectal cancer at Radiation Oncology Victoria to determine its efficacy and the rate of sphincter preservation.Methods:  Sixty‐nine patients (46 men and 23 women) with locally advanced rectal cancer (T3–4 or N1) were treated with preoperative CRT followed by surgical resection of disease. Chemotherapy consisted of either bolus or continuous venous infusion of 5‐fluorouracil (5‐FU). Radiotherapy to a dose of 45 Gy was delivered to the pelvis followed by a boost of 5.4–14.4 Gy in the majority of patients. Surgical resection was carried out 4–8 weeks following completion of preoperative CRT. Univariate and multivariate analyses were performed to examine variables that may influence local recurrence and overall survival rates.Results:  All patients underwent a complete macroscopic resection, including the three patients that had unrecognized distant metastases discovered at the time of operation. Only two patients had microscopic residual disease. Sphincter preservation was achieved in 16 of 25 patients who were thought to require an abdominoperineal resection. Tumour and/or nodal downstaging were achieved in 47 patients (68%), with a pathological complete response in 12 (17%). At a median follow up of 29 months post‐surgery, five patients (7.2%) have developed a local recurrence. Overall 21 patients (30%) have progressed and 12 (18%) have died. Treatment‐related toxicity was acceptable and there was no treatment‐related mortality. There was no significant relationship found between the pathological response to treatment and any clinical endpoint.Conclusions:  Our results confirm the high response rates and acceptable toxicity of preoperative treatment. Further studies are required to better define the impact of preoperative chemotherapy and radiotherapy on long‐term outcomes.