[Effects of decreasing sick leave benefits--results of a survey of Social Health Insurance members]. / Die Auswirkungen von Krankengeldkürzungen--Ergebnisse einer Befragung von GKV-Mitgliedern.

In Germany, a sick employee usually continues to get his wages from his employer for six weeks either in full or reduced. After that period, he only receives "sick benefit payments" (so-called Krankengeld) from the statutory bodies, which, up to 31 December 1996, amounted to 80% of his original gross wage earnings. This has been cut down to 70% of the gross wage earnings effective 1 January 1997. The purpose of this study was to assess the consequences of this general cutdown of sick benefits. A standardised questionnaire was posted to a total of 7,036 female recipients of sick benefit who were members of a South German statutory health insurance body and who resided in various parts of Germany (membership as on 17 December 1996). 2,416 completed questionnaires were returned by 19 February 1997 (= 34.9%). The average daily sick benefit payment dropped from DM 91.95 in December 1996 to DM 82.39 in January 1997, which is equivalent to a sick benefit payment reduction by 10.4 per cent. The average extra cost caused by the illness and not covered by sick benefit amounted to DM 152 per month; one-quarter of the questioned patients were even compelled to pay DM 200 per month extra from their own pocket. Sick benefit recipients must accept a very substantial real monthly income loss. The average income of an employee who is ill for more than 6 weeks is more than a quarter below that of a healthy employee. 78.5% of the questioned persons rated the financial burden and privations caused by the sick benefit cutdown as "extremely heavy" or "considerable". It became evident that the majority of the female patients receiving sick benefit were chronically ill (62.6%). The most frequently reported diseases were diseases of the spine (30.3%) and joints (16.3%), injuries and accidents (14%) and psychiatric illnesses (8.5%). The results of the survey show that the political motive underlying the attempted modification of illness behaviour by means of economic incentives to be healthy, is far removed from reality, for the cutdown of sickness benefit severely affects a group of gainfully employed persons who are in the midst of a deep existential crisis and sorely in need of extensive physical and mental support. From the sociomedical aspect the sick benefit cutdown is highly problematical as far as this group of persons is concerned, since recovery and cure are impeded by measures that lower the status and are experienced as punitive.

Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.

Antisense DNA has shown an ability to target specific oncogene transcripts and inhibit their expression in cells, but the degree to which sustained treatment can suppress total levels of an oncogenic product and alter tumorigenesis in vivo remains to be determined. In this study, NIH-3T3 cells transformed by the activated c-Ha-ras oncogene from T24 human bladder cancer cells were treated for 3 consecutive days in vitro with an antisense DNA pentadecamer complementary to a target in the 5'-flanking region of the c-Ha-ras RNA transcript. Following antisense DNA treatment, a portion of the cells was lysed for measurement of RAS p21 while the remaining cells were evaluated for tumorigeneity by injection s.c. into athymic nude mice at a dose of 5 x 10(5) cells/mouse. The 3 days of treatment with the anti-c-Ha-ras DNA reduced RAS p21 cellular levels by more than 90% while a nonspecific control DNA reduced p21 levels by approximately 20%. Tumor growth of cells treated with anti-c-Ha-ras DNA was significantly reduced for up to 14 days following the end of treatment and implantation into the mice whereas the nonspecific control DNA had no significant effect. These effects on tumor growth were evident in two different strains of nude mice and in both males and females. It is suggested that the pronounced decrease in RAS p21 levels produced by anti-c-Ha-ras DNA resulted in a reversal of the transformed phenotype, and it is this reversal which accounts for the prolonged inhibition of tumorigenesis following antisense DNA treatment.

Direct electrophilic fluorination of tyrosine in dermorphin analogues and its effect on biological activity, receptor affinity and selectivity.

In a preliminary communication we reported [(Tetrahedron Lett. 31, 619 (1990)] that acetyl hypofluorite can be used efficiently to introduce fluorine regiospecifically (ortho to OH) into the phenolic ring of tyrosine-containing peptides. This procedure has been applied to the fluorination of a number of mu-selective opioid peptides derived from dermorphin. While the procedure can be used even when the side chains of Arg, Lys, and Tyr are left unprotected, the sulfoxide of a Met(O)-containing analogue was oxidized to sulfone faster than fluorination of the phenolic ring. This method can also be used when the peptide is attached to Merrifield resin. Thus, Tyr(3-F)-D-Ala-Phe-Gly-NH2 and Tyr(3-F)-D-Arg-Phe-Lys-NH2 (F-DALDA) have been prepared, purified, and characterized. Affinities of these fluorinated peptides for both mu- and delta- opioid receptors are reduced (two- to nine-fold) relative to their nonfluorinated analogues, but their selectivity for mu-opioid receptors is not significantly altered. Similarly, the in vitro biological potencies (GPI and MVD assays) of the fluorinated analogues are reduced (two- to seven-fold) relative to their nonfluorinated parent peptides. Thus, F-DALDA, which has high affinity (Ki mu = 15.2 nM) and selectivity (Ki delta/Ki mu = 5390) for mu-opioid receptors, has potential use in biochemical studies which utilize 19F or 18F- labeled compounds.

Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol.

The 2- and 6-fluoro derivatives of the potent beta-adrenergic agonist 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol were prepared and their adrenergic properties examined. The order of potency was as follows: beta-adrenergic activity (simulation of cyclic AMP formation in C6 glioma cells), 2-F = parent much greater than 6-F; beta 1-activity (rate of contraction, guinea pig atria), parent greater than 2-F much greater than 6-F; beta 2-activity (relaxation of guinea pig tracheal strip), 2-F greater than parent much greater than 6-F. The affinity of the 2-fluoro analogue for beta 1-adrenergic receptors (inhibition of the specific binding of [3H]dihydroalprenolol, rat cerebral cortical membranes) was 2 times greater, while the 6-fluoro analogue was 1450 times less than the parent. These results suggest that the aromatic rings of phenoxypropanolamine adrenergic agonists and phenylethanolamine adrenergic agonists bind in similar fashion to the adrenergic receptor, and that if interactions between fluorine and the side-chain hydroxyl group are critical in defining beta-adrenergic selectivity, the interactions are similar in both phenoxypropanolamines and phenylethanolamines.

[Physiologic nutritional evaluation of complete infant nutrition based on a soybean formula]. / Ernährungsphysiologische Evaluierung von Säuglingsvollnahrungen auf Sojabasis.

The purpose of this review is to evaluate the nutritional quality of soybean-based infant diets on the basis of results published in the scientific literature. Special consideration has been given to the use of soybean protein formulas for infants with reduced intestinal digestion and absorption capacity as well as in cases of cow's milk intolerance and allergic diseases.