Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Carboplatin and radiation therapy for stage IV carcinoma of the head and neck. Preliminary results of a phase II study.

34 patients with head and neck cancer were treated with carboplatin and radiation therapy. Eligibility criteria included stage IV biopsy-proven squamous cell carcinoma with measurable disease and no distant metastases, Karnofsky performance status score of 60 or greater, age 18 years or more, no previous radiation therapy and adequate hematological, renal, and hepatic function. There were 27 males and 7 females. Ages ranged from 44-70 years with a median of 57 years. Follow-up ranged from 11-34 months with a median of 21 months. Total tumor doses ranged from 50-55 Gy with additional boosts of 15-20 Gy. Carboplatin was given in a dose of 100 mg/m2 once weekly (26 patients) and 200 mg/m2 once every 2 weeks (8 patients), during the radiation therapy course in all 34 patients. Each dose of carboplatin preceded irradiation. 25 patients responded while 9 did not. There were 19 complete responses (CR) and 6 partial responses. 4/19 CR recurred and 5/9 non-responding patients died of disease. Mild to moderate nausea and vomiting were seen in 52.3% of patients and mucositis was seen in 61.8% of patients. Moderate to severe hematological toxicity was seen in 35.3% of patients. Response rates and toxicity we observed during this study clearly show that the combination of carboplatin and radiation therapy is effective and suitable for the treatment of patients with stage IV head and neck cancer.     

Metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck.

68 patients with metastatic squamous-cell carcinoma (SCC) of an unknown primary tumor localized to the neck were treated between 1981 and 1990. There were 11 patients treated with radiotherapy alone, 24 patients treated with surgery and radiotherapy and 33 patients treated with radiotherapy and chemotherapy. Male to female ratio was 1.9:1 and the median age was 55 years (range, 33 to 71 years). 41 (61%) patients had N3 disease, 18 (26%) patients had N2 disease and 9 (13%) patients had N1 disease. The majority of N3 patients were treated with radiotherapy + chemotherapy (n = 17) and surgery + radiotherapy (n = 17). The complete response (CR) to radiotherapy + chemotherapy was 73% with 19 patients having no evidence of disease currently. The median survival time (MST of this group was 34+ months. Of the 35 patients who had surgery and/or radiotherapy, 7 (20%) currently have no evident disease. The MST of these two groups (combined) was 22 months. Patients with N3 disease who received radiotherapy + chemotherapy had a higher CR rate and longer MST when compared with those without chemotherapy.     

Competitive reactions of L-methionine and 5'-GMP towards platinum (II) complexes

The complex-formation reactions of the platinum(II) complexes, [Pt(dien)H2O]2+, [PtCl(dien)]+ and [PtBr(dien)]+ (dien is diethylenetriamine) with some biologically relevant ligands such as inosine (INO), inosine-5'-monophosphate (5'-IMP), guanosine-5'-monophosphate (5'-GMP), glutathione (GSH) and L-methionine (S-meth), were studied by UV-Vis (UV-Visible) spectrophotometry and 1H NMR spectroscopy. Reactions of the [PtCl(dien)]+ with L-methionine were studied in the presence and absence of 5'-GMP. The rate constants clearly showed a kinetic preference toward L-methionine. However, competitive reactions of [PtCl(dien)]+ with L-methionine and 5'-GMP demonstrated initially rapid formation of [Pt(dien)(S-meth)]2+ followed by displacement of L-methionine by 5'-GMP. In the later stages the concentration of [Pt(dien)(N7-GMP )]2+ is predominant. The results are analyzed in reference to the anti-tumour activity of Pt(II) complexes.     

Corneal Cellular Immunity in the Guinea Pig

Guinea pigs were sensitized to cornea or skin by grafting or by injection of corneal homogenates in complete Freund's adjuvant. Delayed-type hypersensitivity responses were studied with intradermal skin tests with tissue extracts. Cellular immune responses by lymph node cells (LNC) and peritoneal exudate cells (PEC) were examined in vitro with the thymidine incorporation and macrophage migration inhibition (MIF) assays, and in vivo by passive transfer of delayed-type hypersensitivity. Both the in vivo and in vitro tests demonstrated that animals sensitized either by grafts or parenteral immunization were systemically hypersensitive. Peritoneal exudate cells from animals passively sensitized with either PEC or LNC responded to antigenic stimulation in vitro with MIF production. Furthermore, the skin tests and in vitro assays demonstrated cross reactively with antigens from cornea and skin but not with homogenates from liver.     

Expression of cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis

CONTEXT: Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium. DESIGN: Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features. RESULTS: Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia. CONCLUSION: Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Effects of micronutrient antioxidants (alpha-tocopherol and ascorbic acid) on skin thickening and lung function in patients with early diffuse systemic sclerosis

To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR ≥ 12/year) and decreased lung diffusing capacity (DLCO ≤ 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A—six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m² of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B—seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A–from 18.9/year to 2.2/year, P = 0.03, and in subgroup B–from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0–87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants.