Papillary pneumocytoma of the lung simulating a pleomorphic adenoma

A rare case of papillary pneumocytoma of the lung is reported. The immunohistochemical positivities for EMA, cytokeratin and TTF-l strongly support the hypothesis that the neoplastic cells are originated from type 2 pneumocytes. The tumour also presented areas displaying stroma of non-specific mixoid appearance, simulating a benign tumour of the salivary gland type. We propose that these mixoid areas constitute structures of metaplastic origin.     

Second-line chemotherapy with a hybrid-alternating regimen of bolus 5FU modulated by methotrexate and infusional 5FU modulated by folinic acid in patients with metastatic colorectal cancer pretreated with 5FU. A phase 2 study

BACKGROUND AND AIM: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. RESULTS: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild. CONCLUSIONS: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients.

BACKGROUND: Patients with metastatic colorectal cancer are usually offered systemic chemotherapy as palliative treatment. A multivariate analysis was performed in order to identify predictors and their constellation that allow a valid prediction of the outcome in patients treated with 5-fluorouracil (5-FU)-based therapy. PATIENTS AND METHODS: A total of 3825 patients treated with 5-FU within 19 prospective randomised and three phase II trials were separated into learning (n = 2549) and validation (n = 1276) samples. Data were analysed by tree analysis using the recursive partition and amalgamation method (RECPAM). A predictor could only enter the RECPAM analysis if the number of patients with missing values was < 33.3% within a node, and the minimal node size was set to 50 patients. Twenty-three potential predictors were grouped into subsets of laboratory variables (11 parameters), tumour-related variables (seven parameters) and clinical variables (five parameters). In the first step, tree analysis was performed separately for each predictor subset. The selected prognostic parameters of the resulting partial models (the 'winners') were entered into the general model. The classification rule from the data of the learning set was applied to the independent validation set. RESULTS: Winners of the subgroup analysis for laboratory variables were: platelets > or = 400 x 10(9)/l, alkaline phosphatase > or = 300 U/l, white blood cell (WBC) count > or = 10 x 10(9)/l and haemoglobin < 11 x 10(9)/l, and all predicted a worse outcome. Negative predictors within the subgroup of tumour parameters were: number of tumour sites more than one or more than two, presence of liver metastases or peritoneal carcinomatosis, which predicted a worse outcome. Furthermore, presence of lung metastases, a primary rectal cancer and presence of lymph node metastases all predicted a better outcome in the multivariate setting. Among the clinical parameters only performance status of ECOG 0 or 1 predicted better outcome. In the final regression tree, three risk groups could be identified: low risk group (n = 1111) with a median survival of 15 months for patients with ECOG 0/1 and only one tumour site; intermediate risk group (n = 904) with a median survival of 10.7 months for patients with ECOG 0/1 and more than one tumour site and alkaline phosphatase < 300 U/l or patients with ECOG > 1, WBC count < 10 x 10(9)/l and only one tumour site; high risk group (n = 534) with a median survival of 6.1 months for patients with ECOG 0/1 and more than one tumour site and alkaline phosphatase of > or = 300 U/l or patients with ECOG > 1 and more than one tumour site or WBC count > 10 x 10(9)/l. The median survival times for the good, intermediate and high risk groups in the validation sample were 14.7, 10.5 and 6.4 months, respectively. CONCLUSIONS: Patients can be divided into at least three risk groups depending on the four baseline clinical parameters: performance status, WBC count, alkaline phosphatase and number of metastatic sites. Any molecular or biological marker should be validated against these clinical parameters and decisions for more or less intensive treatments may be studied separately in these three risk groups. Also, clinical trials should be stratified according to the three risk groups.     

The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121)

When overexpressed, the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin receptor (IR) autophosphorylation. A PC-1 variant (K121Q, with lysine 121 replaced by glutamine) is also associated with whole-body insulin resistance when not overexpressed. To better understand the effects of the Q allele on IR function and downstream signaling, we transfected cultured cells with cDNAs for either the Q or the K alleles. In human MCF-7 cells, the Q allele was severalfold more effective (P < 0.05-0.01) than the K allele in reducing insulin stimulation of IR autophosphorylation, insulin receptor substrate-1 phosphorylation, phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell proliferation. Similar data on IR autophosphorylation inhibition were also obtained in mouse R-/hIR and human HEK 293 cell lines. In transfected MCF-7 cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1 receptor autophosphorylation. Both the Q and K alleles directly interacted with the IR, as documented by coimmunoprecipitation assays. This interaction was greater for the Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR interactions are important for the PC-1 inhibitory effect on insulin signaling. In conclusion, the Q allele has stronger inhibitory activity on IR function and insulin action than the more common K allele, and this is likely a consequence of the intrinsic characteristics of the molecule, which more strongly interacts with the IR.     

Double blind, placebo controlled study of nedocromil sodium in asthma

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.     

尼群的平对麻醉犬冠脉流量、心肌耗氧量、二氧化碳产生率的影响

尼群的平20μg/kg iv显著降低麻醉犬血压的过程,冠状窦流量明显增加。持续3h,冠状窦氧含量增加,氧摄取率、心肌耗氧量、二氧化碳产生率降低,持续了3h以上,说明该剂适用于高血压伴心肌缺血。