Receptor status (ER and PgR) determined with histochemical and biochemical methods in breast carcinoma]

Recently, a method similar to ER.ICA has been proposed for the progesterone receptor (PgR) using two monoclonal antibodies, JZB39 and KD68, specific for human PgR and characterized by a molecular weight of 95 and 120 Kd, respectively. A series of 73 breast cancer patients was studied with regards to ER and PgR using both immunocytochemical (ICA) and biochemical (DCC) assays. Results showed no substantial differences between the two methods when considering common clinical-pathological parameters. Overall agreement between ICA and DCC methods was found: 79% for PgR and 78% for ER. A slight quantitative correlation was also observed between the "score values" of the ICA method and the Fmol content of ER and PgR using the Brave-Pearson test (r = 0.49 for PgR; r = 0.43 for ER). Specificity of PgR.ICA method was 77% for PgR and 72% for ER; sensitivity was 82% and 83%, respectively. The ICA method is a reliable technique to assess PgR presence as well as ER. Further studies are necessary to evaluate the prognostic role of nuclear PgR.     

The capsid protein-encoding sequence of foot-and-mouth disease virus O2Brescia

Summary Nucleotide sequences encoding the four capsid proteins of foot-and-mouth disease virus subtype O₂Brescia/1947 have been determined. These and the deduced amino acid sequences were compared with those of a subtype O₁ virus strain. The nucleotide sequences differed at 259 positions, causing only 35 amino acid changes. VP 4 and VP 2 differed by 2.4 and 1.8%, whereas VP 1, known as major viral antigen, and VP 3 differed by 8% and 5.5%, respectively. The differences occur mainly in protein domains not involved in the formation of -helices and -sheets, suggesting that the surfaces of both viruses are more variable than their scaffolds. The O₂Brescia sequence has been submitted to the GenBank data base and has the accession number M 55287.     

Giant aneurysm of the calloso-marginal artery

A giant aneurysm of the right callosomarginal artery is reported in a 3-month-old child. This location is rare: including our case reported here, only three cases have been described. Clinicoradiological findings are presented and the surgical procedure is illustrated.     

Cellular sensitization against sperm and seminal antigens in women

In 13 healthy women and 6 virgins the cellular sensitization against sperm and seminal plasma antigens was demonstrated by an indirect lymphokin assay, the leucocyte migration inhibition test (LMI-test) using the following preparations: "washed" spermatozoa, seminal plasma and spermatozoa of the supernatant prepared with the "swim-up" technique. In both groups of women a cellular sensitization against sperm and seminal plasma antigens could be observed. Further, a dose dependent correlation was found in that way, that increasing concentrations of spermatozoa lead to an increased inhibition of macrophage migration. In virgins cellular sensitization against seminal plasma proteins did not differ from non-virgins, only the percentage of significant reactions in the LMI-Test was reduced. As low sperm concentrations (1 million ml-1), which represent best the physiological situation in the uterus, induced an enhanced migrations of macrophages the enhancement of macrophage migration is considered as physiological cellular sensitization of females against sperm-associated antigens.     

Selection bias in TEFRA at-risk HMOs

The issue of selection bias was investigated using data from 22 HMOs who are enrolling Medicare beneficiaries under Tax Equity and Fiscal Responsibility Act of 1982 (TEFRA) at-risk contracts. The study differs from previously published analyses of this issue in that it deals with the current Medicare risk program (TEFRA) rather than with earlier Demonstration Programs; as an indicator of selection bias, it utilizes beneficiary functional health status at enrollment; and it examines selection not only at the mean of the health status distribution, but at the two tails (very disabled, very able) as well. For each of the participating HMOs, the functional health status of recent Medicare enrollees was compared with that of a control group of randomly chosen fee-for-service beneficiaries. None of the HMOs experienced adverse selection, whether measured in terms of overall (mean) health status of enrollees or in terms of the proportion of the very disabled population that chose to join. Nine of the 22 HMOs were considered to have experienced favorable selection on the basis of the mean health status of new enrollees. In addition, ten more HMOs were found to have experienced favorable selection in one or both tails of the health status distribution. Although a specific cause for the observed enrollment patterns is not identified, speculation is made on factors that may or may not contribute. Evidence suggests that beneficiary self-selection is probably a more important explanation of these patterns than purposeful actions of HMOs to discourage enrollment by sicker beneficiaries (i.e., "skimming").     

An in vitro model for videoimaging of human bladder smooth muscle cell contractions

Knowledge regarding human bladder smooth muscle cell (SMC) physiology is very limited. Only a few specific medical therapies for bladder disorders have therefore been established. The objective of this study was to develop a model for videomicroscopy of bladder SMC contractions. Cells were isolated from human cystoprostatectomy specimens and cultured in a modified EMEM medium. These cells were identified as SMCs by means of immunohistochemistry. For videomicroscopy, the culture flasks were coated with a viscous agent to allow cell contraction. Contractions were visualized by means of a cell culture microscope with a time-lapse videosystem. For cholinergic stimulation of the cells, acetylcholine, in concentrations ranging from 100 μM to 10 mM, was applied. The percentage of contracting cells within the observation field was evaluated for quantitative analysis. In control experiments without contractile stimulant 6% of the cells were observed to contract. Stimulation with acetylcholine induced a significant dose-dependent increase to 47% in contracting cells. These results demonstrated that videomicroscopy is an appropriate tool to investigate the contraction mechanisms of bladder SMCs. This model offers the possibility of studying drug effects on the human detrusor in vitro. Received: 16 September 1999 / Accepted: 1 May 2000     

Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.

PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.