Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses.

We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.     

The clinical manifestations of systemic lupus erythematosus: a Cairo-Glasgow co-operative study.

The clinical features of 78 patients with SLE seen in Cairo and Glasgow are reviewed. Raynaud's phenomenon was recorded more frequently here than in previous series. The value of serial measurements of anti-DNA antibodies, C3 and C4 in the management of SLE is discussed. Although antibodies to native DNA paralleled the disease course in only a minority of SLE patients anti-DNA antibodies were present during all major SLE exacerbations and could be diagnostically useful. Serious systemic infections complicating the management of SLE patients could occur and their diagnosis is discussed.     

Interlaboratory variability of rotational chair test results II: analysis of simulated data.

Standardization of rotational chair testing across laboratories has not been achieved because of differences in test protocol and analysis algorithms. The Interlaboratory Rotational Chair Study Group was formed to investigate these differences. Its first study demonstrated significant variability in calculated results using actual patient data files. No estimation of accuracy could be made, however, because the "true" values of response parameters were unknown. In this study we used simulated "patient" data files to further explore the differences among analysis algorithms. We found a high degree of agreement and accuracy across laboratories using automated analysis of high signal-to-noise/low-artifact data for gain, phase, and asymmetry. Variability increased significantly for the lower signal-to-noise ratio/higher artifact files. Operator intervention generally improved accuracy and decreased variability, but there were cases in which operator intervention reduced accuracy.     

Th-2 type cytokine receptors in allergic rhinitis and in response to topical steroids

Objectives: Th-2 type cytokine production (inter-leukin-4 [IL-4] and interleukin-5 [IL-5]) has been demonstrated to play a significant role in the pathophysiology of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has been shown to reduce the expression of Th-2 type cytokines in vivo. However, the contribution and expression of Th-2 type cytokine receptors in AR and their response to corticosteroid treatment remain to be clarified. Objectives of the current study are 1. To examine the expression of the cytokine IL-4 and IL-5 receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast this with the expression of the receptor for the Th-1 type cytokine, interferon-gamma receptor (IFN-γR), and 2. to examine the effects of pretreatment with topical corticosteroid before allergen challenge on the expression of these same receptors. Study Design: Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment. Methods: Immunocytochemistry (alkaline phosphatase-antial-kaline phosphatase labeling [APAAP] technique) was used to stain nasal biopsy specimens before and after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, MBP, IL-4R, IL-5R, and IFN-γR. Results: Following allergen challenge, we observed a significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P < .05), as well as a significant decrease in the expression of the Th-1 type cytokine receptor (IFN-γR; P < .05). Pretreatment with topical corticosteroids before nasal allergen challenge resulted in decreased expression of IL-4R (P < .05) and IL-5R (P < .05) and increased expression of IFN-γR (P < .05). Further, IL-4R and IL-5R expression correlated with eosinophil infiltration in the tissues. Conclusions: We have demonstrated that in AR, cytokine receptors for IL-4, IL-5, and IFN-γ follow a similar pattern to their ligands. In addition, pretreatment with topical corticosteroids was shown to alter the cytokine receptor expression pattern from a Th-2 profile more toward a Th-1 profile. Laryngoscope, 108:1528–1533,1998     

Realities of respite care.

Respite care in the form of day care centres, in-home respite and institutional care, has been the cornerstone of care for the disabled elderly. Evidence for its effectiveness in helping carers or disabled clients is hard to come by. In this paper, a proposition is put forward for a carefully designed study to answer some of the important points often raised by the providers of such services.     

An exploration of relative health stock in advanced cancer patients.

OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions.     

Cochlear implant outcomes and quality of life in the elderly: Manchester experience over 13 years1

Objectives: To objectively evaluate the clinical and functional outcomes of cochlear implantation in an elderly population. Design: Retrospective comparative study. Setting: Neurotology unit at Manchester Royal Infirmary, a supraregional tertiary referral centre in collaboration with Adult Cochlear Implant Programme at The University of Manchester. Participants: All cochlear implant procedures (38) undertaken on post‐lingually deafened elderly patients (age range at the time of implantation 65–80 years, n = 34) in the period from 1989 to 2002. Main outcome measures: Medical and surgical outcomes. Audiological performance outcomes for isolated words, words in sentences in quiet and noise. Functional outcome measures used are self‐reported measures of the social, psychological and emotional aspects of quality of life, and the differences between expectations for functional outcomes and the realization of functional outcomes. They included expectation profiles, Glasgow Benefit inventory (GBI) and Glasgow Health Status Inventory Questionnaire (GHSI). Results: There was statistically significant improvement post‐implantation of both open and closed set test scores (P < 0.01). Eighty‐two percentage of patients were completely satisfied with their cochlear implants. Patients judged that implantation restored half the loss of quality of life that they had experienced as a result of severe‐profound deafness with a highly significant (P < 0.001) improvement in overall quality of life after implantation. The commonest post‐operative observation was transient mild pyrexia. Conclusions: The age of a cochlear implant candidate should not be a factor in the candidacy decision‐making process. The quality of life of our elderly recipients was significantly improved after cochlear implant.     

Pleural tent after upper lobectomy: a prospective randomized study

Background. The aim of the present study was to assess the cost/efficacy of the pleural tent procedure after upper lobectomy.

Methods. A prospective randomized analysis was performed on 50 patients submitted to upper lobectomy and divided into two groups: group 1 (25 patients) with pleural tent; group 2 (25 patients) without pleural tent.

Results. The univariate comparison between the two groups did not show any significant difference in terms of age, gender, spirometry, smoking history, chronic obstructive pulmonary disease index, side of tumor, arterial oxygen tension, arterial carbon dioxide tension, size and location of tumor, presence of pleural adhesions, length of the stapled parenchyma, and operative time. Pleural tent significantly reduced the days of postoperative air leak (1.2 versus 5.8, p = 0.01), chest tubes (5.4 versus 10.4, p = 0.01), and hospital stay (6.9 versus 10.8, p = 0.01). Moreover, no difference was noted between the two groups in terms of pleural effusion in the first postoperative 48 hours, need of postoperative blood transfusion, and occurrence of other complications.

Conclusions. Pleural tenting after upper lobectomy is a safe and effective procedure and its routine use is warranted.     

Reliability of portal control procedure in irradiation of breast cancer: a Bayesian analysis.

BACKGROUND AND PURPOSE: To determine whether the information gathered from a fixed number of periodic verification films accurately reflects the true imprecision in patient positioning during the whole radiation therapy of early breast cancer. PATIENTS AND METHODS: A total of 204 medial and lateral treatment fields were evaluated in 102 breast cancer patients treated with conservative surgery and radiation therapy. For each treatment field, the central lung distance was measured on portal films obtained from one simulation and four treatment controls at weekly intervals during breast irradiation. Systematic and random errors in patient positioning throughout all treatment fractions were estimated from the available controls using Bayesian methods. RESULTS: The average systematic and random errors during treatment controls were 2.7 and 1.9 mm, respectively. For these mean control values, the probabilities that the true systematic and random errors remain below 5mm during all treatment fractions were 99 and 100%, respectively. CONCLUSIONS: Reproducibility of patient positioning was supported by a virtually null probability for systematic or random errors greater than 5 mm during the whole radiation therapy. Weekly verification films seem to be sufficient to estimate patient positioning errors with high accuracy in radiotherapy of early breast cancer.     

Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma.

PURPOSE: The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGFalpha). PATIENTS AND METHODS: One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. RESULTS: Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. CONCLUSION: Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival.