A new law on advance directives in Germany.

This article presents the new German law on advance directives from 1 September 2009. The history of the parliamentary process of this law is described, the present regulations are explained, their relevance for medical practice discussed and shortcomings are identified. Finally, the new law is compared with other regulations in the international context. Previously established legal practice in Germany has now become largely confirmed by the new law: An advanced directive must be respected in any decision concerning medical treatment, regardless of the stage of the illness. It can be informally revoked at any time, even with limited decision-making capacity. Nobody may be obliged to issue a directive in any way. Advance directives do not need notarisation or routine updating after certain time intervals. Provided that the patient, who is no longer mentally competent, has issued a lasting power of attorney (Bevollmächtiger), or provided that the patient has been appointed a healthcare proxy by the courts (Betreuer), this authorized surrogate must assert the patient's will. The role of the guardianship court is clarified: it only needs to be involved in cases of disagreement as to the patient's will. The new German law thus combines more legal certainty with a liberal emphasis on patient autonomy and flexible, adaptable regulations.

[End-of-life decisions, powers of attorney, and advance directives]. / Entscheidungen am Lebensende, Vorsorgevollmacht und Patientenverfügung.

In modern medicine, decisions about the kind of treatment at life's end are often inevitable. According to German law, powers of attorney and advance directives can be of help in these decisions. When a patient in a state of competence has issued a lasting power of attorney, there is no need for courts to appoint a proxy, and physicians immediately have a legally empowered decision-maker they can address. According to current German law, advance directives are legally valid and binding expressions of a patient's will. They are, however, more powerful when issued after consultation with a physician. If treatment at life's end no longer complies with the patient's will or loses its medical indication, the goal of treatment should be redirected towards palliation. This implies that life-sustaining treatment may be withdrawn or withheld, which is best accomplished with sensitivity to the needs of patients, relatives, and health care professionals.

Sublingual immunotherapy in pollen-induced seasonal rhinitis and conjunctivitis: a randomized controlled trial.

BACKGROUND: Sublingual immunotherapy (SLIT) is a recognized and safe treatment for allergic rhinitis and conjunctivitis. The aim was to evaluate the efficacy and safety of tablets for grass and rye pollen- induced rhinitis and conjunctivitis. METHODS: A double-blind, randomized, placebo-controlled trial was carried out over 9 months. 105 patients received a standardized grass/rye mix extract or a placebo using sublingual drops during the build-up phase. Drops were replaced by sublingual tablets during the maintenance phase (300 IR/daily). RESULTS: In patients that received active treatment, a significantly lower total symptom score (rhinitis and conjunctivitis) compared to the placebo group was observed (p = 0.038). The investigators' assessment revealed a significant improvement in favor of the active treatment group (p = 0.018). Skin reactivity to grass and rye pollen was significantly reduced in the active treatment group (p < 0.05). No statistical difference was observed between the two groups for serum-specific IgG4 levels. Side effects were local and mild, and no severe systemic reactions were reported. CONCLUSION: This study indicates that tablet-based sublingual immunotherapy was safe and significantly improved grass/rye pollen-induced rhinoconjunctivitis symptoms. It was also associated with a significant inhibition of the immediate skin response.

Decreased releasability of basophils from patients with cold urticaria after cold exposure.

Histamine release from peripheral blood basophils challenged with C5a, f-met-peptides and calcium ionophore was studied in patients with cold urticaria before and after exposure to low environmental temperatures. Compared to healthy controls, stimulated mediator release before cold exposure was increased in 7 of 11 patients. When challenged by cold exposure mediator release from in vitro-stimulated basophils was decreased. This decrease was more pronounced after stimulation with receptor-mediated stimuli (e.g. C5a) as compared to receptor-unrelated stimuli, e.g. calcium ionophore. In 4 of 11 patients stimulated mediator release before cold exposure was moderately increased. Also after cold exposure only a weak decrease of stimulated histamine release was seen. Levels of activated complement components (C3a) before and after cold exposure failed to provide evidence for complement activation in vivo. Also the number of circulating basophils as well as their cellular histamine content remained normal after cold exposure. The results show that in these patients release of histamine is altered before and after cold exposure. These changes in basophil responsiveness are not due to complement activation in vivo.

Changes in erythrocyte permeability due to palytoxin as compared to amphotericin B.

Palytoxin causes within minutes a temperature-dependent K+ loss from human and rat erythrocytes which is followed within hours by haemolysis. It decreases the osmotic resistance in a concentration-dependent manner, so that osmotic influences are negligible for K+ release but considerable in haemolysis. External K+ inhibits the haemoglobin release and Rb+ inhibits the release of K+ and haemoglobin. Ca2+ (over 20 microM) and borate (over 5 microM) enhance the loss of K+ and haemoglobin. With both Ca2+ and borate present, the efficacy of palytoxin is raised about 10 000-fold. Under these conditions, about 15 palytoxin molecules per human cell trigger a 50% K+ loss over a wide range of cell concentrations. The palytoxin effect is reversible. After depletion from K+ by low concentrations of palytoxin, human cells can be refilled with K+ and resealed. The pores formed by palytoxin are small. They allow the entrance of Na+ and choline, whereas inositol is largely excluded and Ca2+, as well as sucrose and inulin, are completely excluded. Amphotericin B resembles palytoxin in its ability to cause a considerable prelytic K+ loss and to form small pores. However, it is about 1000-times weaker than palytoxin, is not inhibited by K+ or Rb+, is not activated by Ca2+ or borate, and has a negative temperature dependence. Thus palytoxin represents a novel type of cytolysin.