Aims  To measure and compare the systemic bioavailability of fluticasone propionate aqueous nasal spray and a new nasal drop formulation, using a sensitive analytical method and high dose regimen. Methods  Volunteers received four 800 µg doses of fluticasone propionate as a nasal spray or drops over 2 days, separated by an 8 h dose interval. On day 2, blood samples were collected for assay of fluticasone propionate plasma concentrations. Results  The mean systemic exposure, for both formulations was 8.5 pg ml−1 h (drops) and 67.5 pg ml−1 h (spray). Mean absolute bioavailabilities were estimated to be 0.06% (drops) and 0.51% (spray), by reference to historical intravenous data. Conclusions  Both formulations exhibited low systemic bioavailability, even at 12 times the normal daily dose. The bioavailability from the nasal drops was approximately eight times lower than from the nasal spray.

Rats given an intravenous injection of Sephadex particles (0.5 mg of G200 in 1 ml of saline) on days 0, 2 and 5 had a blood eosinophilia which was maximal on day 7. On day 7, broncho‐alveolar lavage (BAL) fluids taken from the rats contained an increased number of eosinophils and fewer mononuclear cells but there was no change in the small number of neutrophils. In addition the rats were hyper‐sensitive to the increase in resistance to artificial respiration produced by 5‐hydroxytryptamine (5‐HT), given intravenously, with a shift to the left of the log dose‐response curve. Lung parenchymal strips, taken from the rats on days 6, 7 and 8, were hyper‐reactive to 5‐HT with an increase in slope of the log dose‐response curve. Compounds with a wide variety of activities were evaluated for their effects on the blood eosinophilia on day 7 when given before each injection of Sephadex. The eosinophilia was reduced by glucocorticosteroids, β‐adrenoceptor agonists, aminophylline, dapsone and phenidone. Dexamethasone, isoprenaline, dapsone and phenidone at doses that reduced the blood eosinophilia also reduced the changes in number of leucocytes in the BAL fluids and the hyper‐responsiveness to 5‐HT in vivo and in vitro, except that the effects of dapsone on the hyper‐sensitivity to 5‐HT in vivo did not reach significance. Aminophylline was the least effective of the drugs at reducing the blood eosinophilia and its effects on the other changes did not reach significance. Sodium cromoglycate reduced the BAL eosinophilia but had no effect on the other changes produced by Sephadex. The correlation coefficients between blood eosinophil numbers and reactivity to 5‐HT in vitro and sensitivity in vivo were r = 0.76, (n = 88; P > 0.001) and r = 0.53, (n = 61; P > 0.001) respectively. Doses of dexamethasone, isoprenaline, dapsone and phenidone that reduced the blood eosinophilia when given before each injection of Sephadex were inactive when given up to 8 h after the Sephadex. These data show an association between blood eosinophilia and hyper‐responsiveness of the lung. The blood eosinophilia in the rats was triggered within the first few hours of injecting the Sephadex and drugs have been identified which inhibit this trigger.

FPANS and BUD RPD are effective therapies with a good safety profile for the treatment of perennial rhinitis but, in this direct placebo-controlled comparison, FPANS was more efficacious than BUD RPD, and the patients preferred the ANS device to the RPD.

In rats, Sephadex treatment on days 0, 2 and either 4 or 5 resulted in a blood and lung eosinophilia, an increase in lung cell fragility, an increase in the functional activity of peritoneal eosinophils in vitro and a sustained increased responsiveness of lung parenchymal strips to KCl, 5-hydroxytryptamine (5-HT) and carbachol that was not associated with oedema or gross fibrosis. The corticosteroid dexamethasone, when given before each injection of Sephadex, reduced all these effects of Sephadex. When given 30 min after the last injection of Sephadex, dexamethasone had no effect on the number of blood and lung eosinophils but it did reduce the functional activity of peritoneal eosinophils, the increased lung cell fragility and the hyperresponsiveness to 5-HT. Repeated administration of dexamethasone to rats with an established hyperresponsiveness that was no longer associated with cellular inflammation had minimal effects on this hyperresponsiveness.

studied in Minneapolis in a group of 2,523 volunteer women. There was an unacceptably large group wherein the thermogram was read as abnormal but no lesion could subsequently be proved. The reliability of the method was inadequate, since out of four patients diagnosed as having breast cancer, only one was found by thermogram. The examining physician diagnosed two of the lesions as suspicious and these were missed by the thermographic technique. The remaining lesion was missed by the examining physician and an initial reading of the thermogram as suspicious was changed to normal. The presence of technical difficulties and inability to examine women with large, pendulous breasts seemed to further invalidate this method as a logical screening procedure.That cancer is a continually increasing problem for our constantly enlarging geriatric popula¬ tion has been shown in statistics of the American Cancer Society reporting the number of annual cancer deaths. Between 1930 and 1960 the total cancer deaths in the United States has risen from 118,000 to 227,000. If the present cancer mortality continues, projected estimates indicate that by the year 2000 (32 years from now) we will have 324,000 patients dying per year of cancer in the United States.Recent studies indicate painfully small progress has been made in the overall survival from breast cancer during the past 50 years. When cancer in-cidence and mortality was studied in Minneapolis for two comparable periods one decade apart (1941 to 1943 as compared with 1951 to 1953). Gunlaugson et al showed that with age-adjusted rates there had been a significant decrease in mortality for most cancers, an increase in deaths from lung can¬ cer, but the mortality figures for cancer of the breast remained exactly the same.1 Other large pop¬ ulation studies have shown similar results.It is obvious upon critical review of the breast cancer problem that a new approach is needed, either through earlier and better diagnosis of oc¬ cult disease or with more effective therapy, if re¬ sults are to improve significantly in our era.For many years the correlation between breast tumor size to patient cure and survival has been debated. In one study, performed between the dec¬ ade 1936 to 1946, Haagensen showed that for le¬ sions of 2 mm to 3 cm the five-year clinical cure rate was 62.5%: in comparison, when lesions were over 7 cm in diameter at surgery there was a five-year clinical cure rate of 7.6%.' Many clinicians have considered manual palpation of the breast grossly inadequate for early detection of occult breast cancer. With this thought in mind our study was initiated to compare the effectiveness of thermo¬ graphie scanning of the female breast to a physi¬ cian's manual breast examination for detection of early, occult lesions.3,4The Problem and Clinical Experiment Our problem as posed to this community was, "can occult cancer of the breast be detected by a mass screening method, such as thermography, which would be reliable, simple, and inexpensive?" We proposed to clinically determi...