[Cost-Effectiveness of the 21 Gene Assay in Patients with Node-Positive Breast Cancer]. / Wirtschaftlichkeit des 21 Gene Tests in der Behandlung von Patientinnen mit nodal-positivem Mammakarzinom.

Aim: Breast cancer is the most common type of cancer for women. Most guidelines recommend patients with lymph-node positive (LN+) early stage breast cancer to undergo adjuvant chemotherapy to prevent or delay distant recurrence. This may lead to frequent, general usage of chemotherapy accompanied with high costs and side effects. The Oncotype DX, also called 21 Gene Assay, by Genomic Health is a genomic test which predicts the individual risk of breast cancer recurrence as well as the benefits of chemotherapy. Economic analyses have indicated the cost-effectiveness of the 21 Gene Assay for patients with LN- breast cancer. This paper discusses recent research on the cost-effectiveness of using this assay for patients with LN+ breast cancer. Methods: A systematic literature research was undertaken using the following databases: Pubmed, Embase, Business Source Complete and EconLit. Studies found were analysed for study design, parameters, and analysis of uncertainty. The transferability of the results to Germany was examined using a list of criteria. Results: 7 relevant economic analyses were identified. Incremental cost-utility ratios ranged from cost-savings of € 3 548 per patient to additional costs of € 9 113 per QALY gained. The transferability of the results to Germany is limited particularly by differences in the medical cost approach, in absolute and relative prices in health-care, and by practice variation. Conclusion: There is evidence that the cost-utility of the assay when used for LN+ breast cancer is basically comparable to that for the use with the LN- type. More precise results for Germany would require valid data on the risk of recurrence as well as on the description and evaluation of health-related quality of life of patients.

[Costs of illness for asthma and COPD in adults in Germany]. / Krankheitskosten für Asthma und COPD bei Erwachsenen in der Bundesrepublik Deutschland.

UNLABELLED: BACKGROUND; Asthma and COPD have a high and growing epidemiological impact worldwide, and it is often indicated that significant economic costs are linked to this. The aim of this review is to estimate the cost-of-illness for both diseases for adults in Germany. METHODS: A systematic search of Pubmed, Embase, EconLit and Business Source Complete was performed for the years 1995-2012 to identify German cost-of-illness studies for asthma and COPD in German or English language. 6 studies for asthma, 7 studies for COPD and 1 for both diseases met the inclusion criteria. The results of the identified studies were extrapolated to 2010 prices and compared within the same disease. RESULTS: In spite of the heterogeneity in methodology and results, medication was identified as the most important component of direct costs and work loss as the most important component of indirect costs. All in all, the estimated costs per case of illness and year for asthma sum up to 445 to 2 543 € and for COPD to 1 212 to 3 492 €. CONCLUSION: The analysed cost-of-illness studies confirm that asthma and COPD are costly but results vary markedly. COPD due to its higher costs per case and its similar prevalence causes higher macroeconomic costs. Our results emphasise the economic relevance of prevention and disease management for these lung diseases.

Real-time breath gas analysis for pharmacokinetics: monitoring exhaled breath by on-line proton-transfer-reaction mass spectrometry after ingestion of eucalyptol-containing capsules.

Eucalyptol (1,8-cineole) is a common active agent in non-prescription pharmaceutical products that is employed to clear the airways during mucus blockages. Following ingestion of a eucalyptol-containing capsule, the capsule dissolves in the gut and transfers eucalyptol into the blood, which is subsequently expelled via the lungs, thus exposing this decongesting and inflammation-abating compound to the airways. The breath gas concentrations of eucalyptol in 11 healthy adult volunteers were monitored at regular intervals after capsule ingestion using on-line proton-transfer-reaction mass spectrometry (PTR-MS). Eucalyptol appeared in exhaled breath gas at varying times following ingestion, with its onset ranging from 1 h and 6 min to 4 h and 48 min (mean ± SD: 2.1 ± 0.5 h). Maximum concentrations also varied greatly, with peak eucalyptol levels between 106 and 1589 ppb(v) (mean ± SD: 489 ± 319 ppb(v)). These variations were not only inter-subject, but also intra-subject, i.e. repeated tests with the same participant yielded different onset times and a broad range of concentration maxima. A considerable contribution to these variations from infrequent sampling and analysis is discussed. This study characterized the temporal transfer of eucalyptol via the blood into the airways by examining exhaled breath and thereby demonstrated the suitability of on-line breath gas analyses, particularly PTR-MS, for certain pharmacokinetic investigations.

Glycosylphosphatidyl inositol-anchored proteins and fyn kinase assemble in noncaveolar plasma membrane microdomains defined by reggie-1 and -2.

Using confocal laser scanning and double immunogold electron microscopy, we demonstrate that reggie-1 and -2 are colocalized in < or =0.1-microm plasma membrane microdomains of neurons and astrocytes. In astrocytes, reggie-1 and -2 do not occur in caveolae but clearly outside these structures. Microscopy and coimmunoprecipitation show that reggie-1 and -2 are associated with fyn kinase and with the glycosylphosphatidyl inositol-anchored proteins Thy-1 and F3 that, when activated by antibody cross-linking, selectively copatch with reggie. Jurkat cells, after cross-linking of Thy-1 or GM1 (with the use of cholera toxin), exhibit substantial colocalization of reggie-1 and -2 with Thy-1, GM1, the T-cell receptor complex and fyn. This, and the accumulation of reggie proteins in detergent-resistant membrane fractions containing F3, Thy-1, and fyn imparts to reggie-1 and -2 properties of raft-associated proteins. It also suggests that reggie-1 and -2 participate in the formation of signal transduction centers. In addition, we find reggie-1 and -2 in endolysosomes. In Jurkat cells, reggie-1 and -2 together with fyn and Thy-1 increase in endolysosomes concurrent with a decrease at the plasma membrane. Thus, reggie-1 and -2 define raft-related microdomain signaling centers in neurons and T cells, and the protein complex involved in signaling becomes subject to degradation.

Targeted ablation of NrCAM or ankyrin-B results in disorganized lens fibers leading to cataract formation.

The NgCAM-related cell adhesion molecule (NrCAM) is an immunoglobulin superfamily member of the L1 subgroup that interacts intracellularly with ankyrins. We reveal that the absence of NrCAM causes the formation of mature cataracts in the mouse, whereas significant pathfinding errors of commissural axons at the midline of the spinal cord or of proprioceptive axon collaterals are not detected. Cataracts, the most common cause of visual impairment, are generated in NrCAM-deficient mice by a disorganization of lens fibers, followed by cellular disintegration and accumulation of cellular debris. The disorganization of fiber cells becomes histologically distinct during late embryonic development and includes abnormalities of the cytoskeleton and of connexin50-containing gap junctions. Furthermore, analysis of lenses of ankyrin-B mutant mice also reveals a disorganization of lens fibers at postnatal day 1, indistinguishable from that generated by the absence of NrCAM, indicating that NrCAM and ankyrin-B are required to maintain contact between lens fiber cells. Also, these studies provide genetic evidence of an interaction between NrCAM and ankyrin-B.

Chlorate as an inorganic disinfection by product in swimming pools.

Chlorate and chlorite concentrations were determined in water samples taken from 33 swimming pools. In the pools under investigation, disinfection of the water is carried out either by gaseous chlorine (n = 14) or hypochlorite solution in conjunction with flocculation and sand filtration. A number of the pools also use ozone treatment to augment the disinfection process. Chlorite was not detectable in any of the samples (detection limit 1 mg/l). High concentrations of chlorate were detected in samples from a number of the pools; in one case as high as 40 mg/l. Higher chlorate concentrations were found to be associated with those pools using hypochlorite solution as a disinfecting agent. In contrast, relatively low chlorate concentrations were found in pools treated with gaseous chlorine. In order to elucidate any relationship between the chlorate content of pool water and that of the respective hypochlorite stock solution, chlorate and bromate concentrations were determined in the hypochlorite stock solutions of nine pools. Bromate concentration in the stock solutions were not found to exceed 1.2 g/l, chlorate was measured in concentrations of up to 44.5 g/l. The additional use of ozone as part of the water purification process appears to have no significant influence on chlorate concentration. Chlorate has no bactericidal properties and does not interfere with the measurement of certain parameters relevant to hygiene in swimming pools such as free and combined chlorine, pH or redox potential. At present, the effects of high chlorate concentrations in swimming pool water are unclear. Our initial investigations indicate that chlorate has no cytotoxic (Neutral-Red assay) or irritating properties (HET-CAM assay). However, both chlorate and chlorite are known to interfere with the haematopoetic system. In Germany, the MCL for chlorite in drinking water is 0.2 mg/l. It is therefore strongly recommended that measures should be taken to reduce chlorate concentrations in swimming pool water.

[Irritating effects of disinfection by-products in swimming pools]. / Irritierende Wirkung von Nebenprodukten der Schwimmbadwasserdesinfektion.

Compounds which can occur as disinfection by-products (DBP's) in swimming pool water were examined for their mucous membrane irritating potential. Previous studies using the rabbit eye test (Draizé test) have shown that the irritating potential of typical concentrations of free and combined chlorine are insufficient to explain the degree of eye irritation that can result from exposure to swimming pool water. Other DBP's which may be responsible for eye irritation include halogenated carboxyl compounds (HCC's) which act as precursors during the formation of chloroform. In this study, a modified HET-CAM Test (Hens Egg Test at the Chorion Allantois Membrane) has been used to investigate the mucous membrane irritating effects of HCC's. Some of the compounds tested were found to have a significantly increased irritating effect when compared to a chlorine/chloramine mixture of the same concentration, several mixtures of HCC's where even more active at lower concentrations than single compounds. However, the irritating effects of individual compounds as well as of mixtures of HCC's were not sufficiently intense to allow the identification of those compounds specifically responsible for the overall observed increase in irritation. HCC's were therefore tested in the presence of aqueous chlorine solution. When combined with aqueous chlorine, a number of compounds exhibited significantly enhanced effects. Our results show that the eye irritating effects of low concentrations of DBP's can be investigated using a modified HET-CAM assay. Moreover, results obtained using this assay suggest that the mucous membrane irritating potential of swimming pool water is a consequence of the effects and synergistic action of a number of DBP's in the presence of chlorine. Further work should be carried out in order to establish an indicator for eye irritating effects of swimming pool water.

[Potassium as an indicator of anthropogenic contamination of swimming pool water]. / Kalium als ein Indikator der anthropogenen Belastung von Schwimmbadwasser.

Swimming pool water is processed, filtered and disinfected repeatedly in order to maintain hygienic conditions. Additionally, fresh water is added. However, it cannot be avoided, that the concentrations of certain components of swimming pool water will increase in the course of time. DIN 19,643 regulates that fresh water supply can be measured by nitrate concentration. Nitrate is mainly formed by oxidation of nitrogen containing organic compounds. Oxidation reactions are complex and the amount of nitrate formed by this process depends on specific factors which may vary in swimming pools with different technical equipment. Therefore nitrate is only of limited reliability to estimate fresh water addition in public swimming pools. Main sources for nitrogen containing compounds in pool water are sweat and urine which contain inorganic compounds like potassium. Potassium is a direct indicator of contamination. Its concentration is not influenced by chemical reactions because it is an inert compound. The urine release into the water of indoor pools was estimated by this parameter to be 77.5 ml/person, in outdoor pools about 60 ml. Potassium concentration in swimming pools will reach an equilibrium concentration, depending on the size of the pool, the number of bathers and the amount of fresh water added. This equilibrium concentration is mathematically calculated in a general approach. In none of 36 swimming pools where potassium concentration was measured, this calculated value was exceeded. The results indicate that the potassium concentration is a new valuable parameter to assess the quality of swimming pool water under hygienic aspects.

[Haloforms in hot spring pools]. / Haloforme in Warmsprudelbecken. Haloforms in Spas.

Chloroforme is formed during disinfection of swimming pool water in certain amounts depending on several cofactors. Because of its carcinogenic properties this compound has been frequently a subject of public discussion over the last couple of years. Little is known about chloroforme concentrations in spas. Spas are operated at significantly higher temperatures as compared to other pools, and the organic contamination may be higher. Therefore, chloroforme is possibly produced in higher amounts than in regular swimming pools. On the other hand the air that is blown through the bassin may reduce the concentration of this low volatile substance. In order to investigate the average concentration, 21 water samples from spas in public indoor pools were analyzed as to their chloroforme contend. The median of concentration was 3.8 micrograms/l. The maximum measured chloroforme concentration was 6.4 micrograms/l. The average chloroforme concentration in the filtered water was slightly higher than before filtration. The use of spas does not implicate an increase in chloroforme uptake by bathers.

[Hormones and venous system]. / Hormones et système veineux.

Sex hormones have an effect on venous "content" and "container" according to their chemical nature, their dosage and their mode of administration: 17 beta-estradiol (endogenous): protective effect; synthetic estrogens, at normal or low doses: thrombogenic; oral natural estrogens: thrombogenic; extra-digestive natural estrogens: non thrombogenic; non steroid progestagens (androgenic): thrombogenic; non androgenic progestagens: non thrombogenic. Clinically, the venous disease si characterized by sudden episodes occurring at key-periods of the hormonal life: puberty, pregnancy, menopause, oral contraceptives intake, substitute treatments of menopause, premenstrual syndrome. Evaluation of these different situations shows that an early treatment is possible and needed, which, although not providing a new venous wall for these constitutionally fragile patients, may act effectively at two levels: 1) correction of the haemodynamic disorder (venous reflux in the saphenous arches and the perforators; 2) resorption of tissue infiltration. As primary prevention, in a patient with hormonal disorders or who must be treated with estrogens or progestagens, the objective of our treatment is to protect the venous wall and encourage the return circulation. One must: 1) reinforce the vaso-constrictive effect and the parietal tone, 2) limit collagen and elastin alteration, 3) reinforce capillary permeability and decrease the interstitial edema, 4) normalize the haemorheological constants, 5) restore the balance hemostasis-fibrinolysis. The opinion of a phlebologist seems essential before prescribing a hormonal treatment and monitoring the effects of the treatment. Cooperation between gynaecologists and phlebologists is particularly essential in the interpretation of the clinical disorders as well as discussing the venous risk, the dosage and the administration route of sex hormones.

[Effect of coenzyme A (COA) on the 6-keto-prostaglandin F1 alpha content of the aorta of rats made diabetic with streptozotocin. Potential mechanism of action of its favorable effect on microcirculatory disorders in man]. / Influence du coenzyme A (COA) sur la teneur en 6 ceto prostaglandine F1 alpha d'aortes de rats rendus diabétiques par la streptozotocine. Mécanismes d'action possible de son effet bénéfique sur les perturbations microcirculatoires chez l'homme.

The production of 6-keto-prostaglandin F1 alpha, a stable metabolite of the vasodilator prostacyclin (PGI2), by fragments of the thoracic aorta of rats made diabetic by streptozotocin, was evaluated by radio-immunological assay. The level of production was found to be statistically higher (p less than or equal to 0.01) in the group treated with Coenzyme A (CoA) than in the placebo group. The authors suggest that the mode of action of CoA 1000 much greater than in microcirculatory pathology could involve an increased production of vasodilator prostacyclin.

[Modification of the level of adenosine triphosphate in digital pulp capillary blood in patients with microcirculatory disorders following i.v. injection of coenzyme A (CoA 1000)]. / Modification du taux d'adénosine tri-phosphate (ATP) dans le sang capillaire prélevé au niveau de la pulpe digitale, dans les troubles de la microcirculation, après injection i.v. de coenzyme A (CoA 1000).

Capillary blood ATP assay was performed in 2 groups of patients (diabetic and non-diabetic) with disorders of microcirculation, before and several minutes after 2 mg I.V. of Coenzyme A (CoA 1000). Values obtained showed a significant increase in both groups. The hypothesis advanced, based on previous experimental data indicating an action of CoA on intracellular calcium movement, is that CoA 1000 acts by elevation of the membrane ATP/Ca+ ratio of red corpuscles, and possible activation of their deformability and flow rate in the microcirculation.