Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.     

Phase III clinical trial with a new oral contraceptive containing 150 micrograms desogestrel and 20 micrograms ethinylestradiol.

Results are presented of a Phase III international multicentre trial to study the effect of a new low-dose oral contraceptive (OC) containing 20 micrograms ethinylestradiol and 150 micrograms desogestrel (Mercilon) regarding efficacy, cycle control, blood pressure, and acceptability. Altogether 1,684 women from 12 European countries were included in the study. Four pregnancies occurred, 3 of them patient failures, one tablet failure. The overall Pearl Index was 0.20. The frequency of irregular bleeding was comparable to that recorded with other commonly used low-dose OCs. No serious side effects occurred. The incidence of the most frequently reported subjective side effects--headache, nausea and breast tension--was already low after the first cycle of treatment and decreased to below pretreatment levels with continued use. There was a small increase in mean body weight, which was confined essentially to young women. The preparation did not affect the mean systolic or diastolic blood pressure. This new preparation has thus proved to be an effective, safe and well-accepted ultra low-dose oral contraceptive.     

Dependence of vitamin B-6 status assessment on alcohol intake among elderly men and women (Dutch Nutrition Surveillance System)

To obtain more insight into the effect of moderate alcohol intake on vitamin B-6 status indicators, we studied the associations of alcohol intake (unadjusted and adjusted for intake of vitamin B-6 and protein) with the erythrocyte aspartate aminotransferase activation coefficient (EAST-AC) and plasma pyridoxal 5'-phosphate (PLP) level. Data obtained from men (n = 224) and women (n = 217) aged 65-79 (nationwide sample in the Netherlands) were used for this purpose. Although alcohol intake (a maximum of 21% of the energy came from alcohol) tended to be positively associated with PLP, this association never reached statistical significance (p greater than or equal to 0.05). EAST-AC was inversely associated with alcohol intake, whether or not it was adjusted for vitamin B-6 and protein intake. Similar results were found for the total EAST activity (after adding PLP) or apoenzyme activity; the basal EAST activity (before adding PLP) or holoenzyme activity was not associated with the alcohol intake. These results indicate that caution is needed in the interpretation of the specificity of EAST-AC (i.e., the degree to which EAST-AC is unaffected by other factors) as an indicator of vitamin B-6 intake.     

Evolution of white matter lesions in neurofibromatosis type 1: MR findings.

To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm.     

Lärm auf Intensivstationen Ein Beitrag zur Lärmreduktion durch Modifikation der Atemgasbefeuchtung

Today, noise pollution is an evident and ubiquitous problem even in intensive care units. Noise can disturb the physiological and psychological balance in patients and staff. Especially intubated patients and those breathing spontaneously through a T-piece are exposed to the noise emitted by the nebuliser used to humidity the respiratory gas. This may make patients feel uncomfortable. To reduce noise pollution in the ICU a modified T-piece has been developed and investigated. In order to heat and humidity the respiratory gas a Conchaterm III unit (Kendall company) and a thermo flow cylinder (De Vilbiss company) is necessary. While respiratory gas is flowing, water is sucked out of the heated thermoflow cylinder and nebulised according to the Venturi-Bernoulli principle. To adjust the oxygen concentration of the respiratory gas a plastic ring must be turned to either close (98% oxygen) or open a valve allowing room air to mix (40% oxygen). Noise pollution of the unit varies with admixture of room air. With a new device – a special oxygen – air mixing chamber – the oxygen concentration of the respiratory gas can be adjusted outside the thermoflow cylinder, hardly producing any noise pollution. Therefore the principle of nebulisation could be changed to humidification. A thermoflow cylinder without the nebulisation unit allows the respiratory gas to flow through the thermoflow cylinder over heated and evaporating water, hardly causing any noise pollution. In both types of T-pieces the temperature of the respiratory gas is controlled and corrected by the Conchaterm unit. As the result of these modifications, noise pollution has been reduced from 70?dB(A) to 55?dB(A). In the modified T-piece, the quality of humidification has been evaluated with a fresh gas flow of 22?l/min and at a gas temperature of 37°?C, not only collecting condensed water but also lost water. The modified T-piece allows a physiological humidification of the respiratory gas. The modified T-piece is a simple and efficacious substitute. Patients and staff are protected from adverse noise effects and patient well-being might be improved.     

Chondrocyte nonresponsiveness of arthritic articular cartilage caused by short term immobilization

We studied the effect of short term immobilization on chondrocyte synthetic function. Arthritis from intraarticular injection of either glucose oxidase or interleukin 1 (IL-1) led to suppression of proteoglycan synthesis. Extension casting of arthritic knees prevented inhibition of proteoglycan synthesis, whereas later casting restored synthesis to normal. During chronic antigen induced arthritis casting protected chondrocyte synthesis for a period of 5 days. The chondrocyte nonresponsiveness was not from altered penetration of suppressing substances. Radiolabelled biologically active IL-1 showed no difference in retention or localization in articular cartilage of either mobile or immobile knees. Flexion casting did not induce unresponsiveness of chondrocytes and suppression of synthesis was similar to that in mobile arthritic knees, indicating the importance of loading. The nonresponsiveness occurred only during immobilization and rapidly disappeared after removal of the cast, provided that suppressing agents were still present. Thus, during short term immobilization chondrocytes are protected from inhibition of proteoglycan synthesis by suppressing agents. This protection may benefit repair of the depleted cartilage matrix with waning inflammation.