[Patients' rights--doctors' duties]. / Patientenrechte--Arztpflichten (I).

On 26 February 2013 the new "Law on Patients' Rights" (hereinafter also the "Law") became effective. This Law strengthens patients' rights vis-à-vis the insurdnce company and also regulates patients' rights regarding their relation to the doctor. This has consequences for the laws on medical liability all doctors must consider. The doctor's performance is and remains a service and such service does not hold any guarantee of success. Nevertheless, this Law primarily reads as a "law on the duties of physicians". To duly take into account these duties and to avoid mistakes and misinterpretation of the Law, the Ethics Committee of the Consortium of Osteosynthesis Trauma Germany (AOTRAUMA-D) has drafted comments on the Law. Brief summaries of its effects are to be found at the end of the respective comment under the heading "Consequences for Practice". The text of the law was influenced particularly by case law, as continuously developed by the German Federal Court of Justice ("BGH"). The implementation of the Law on Patients' Rights was effected by the newly inserted sections 630a to 630h of the German Civil Code (the "BGB"), which are analysed below. The following comments are addressed to physicians only and do not deal with the specific requirements and particularities of the other medical professions such as physiotherapy, midwifery and others so on. Special attention should be paid to the comments on the newly inserted Duty to inform, which has to be fullfilled prior to any diagnostic or therapeutic procedure (sec. 630c para 2 sentence 1 BGB). Under certain conditions the doctor also has to inform the patient about the circumstances that lead to the presumed occurance of a therapeutic or diagnostic malpractice (sec. 630c para. 2 sentence 2 BGB), based on the manifestation of an undesired event or an undesired outcome. As before, the patient's valid consent to any procedure (sec. 630d BGB) is directly linked to the comprehensive and timely provision of information (sec. 630e BGB). Comprehensive documentation obligations regarding all procedures are stipulated in sec. 630f BGB. As before, the burden of proof still rests with the patient, unless a severe malpractice has been established (sec. 630h BGB). The definition of "severe malpractice" remains unchanged and is based on the case law of the Federal Court of Justice (BGH). The patient's obligations to preserve his or her health and to actively support the process of recovery and securing a positive outcome of the treatment are not explicitly mentioned in the Law. Nevertheless, the patient and the physician need to work closely together to achieve a successful result of the treatment. In case the patient does not give his or her cooperation, the physician should consider terminating the treatment relationship.

Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice.

Intranasal or intramuscular (i.m.) immunization of mice and i.m. immunization of rabbits with formalinized staphylococcal enterotoxin B (SEB) toxoid in saline elicited higher anti-SEB serum immunoglobulin G (IgG) titers when the toxoid was formulated with proteosomes. In addition, intranasal immunization of mice with this proteosome-toxoid vaccine elicited high levels of anti-SEB IgA in lung and intestinal secretions, whereas the toxoid without proteosomes did not. Two i.m. immunizations with proteosome-toxoid plus alum also induced higher murine serum responses than alum-adjuvanted toxoid without proteosomes. Furthermore, proteosome-toxoid delivered intranasally in saline or i.m. with either saline or alum afforded significant protection against lethal SEB challenge in two D-galactosamine-sensitized murine models of SEB intoxication, i.e., the previously described i.m. challenge model and a new respiratory challenge model of mucosal SEB exposure. Efficacy correlated with the induction of high serum levels of anti-SEB IgG. In contrast, intranasal or i.m. immunization with toxoid in saline without proteosomes was not significantly protective in either challenge model. Proteosome-toxoid plus alum given i.m. also elicited more significant protection against respiratory challenge than the alum-adjuvanted toxoid alone. The capacity of proteosomes to enhance both i.m. and intranasal immunogenicity and efficacy of SEB toxoid indicates that testing such proteosome-SEB toxoid vaccines in the nonhuman primate aerosol challenge model of SEB intoxication prior to immunogenicity trials in humans is warranted. These data expand the applicability of the proteosome mucosal vaccine delivery system to protein toxoids and suggest that respiratory delivery of proteosome vaccines may be practical for enhancement of both mucosal and systemic immunity against toxic or infectious diseases.

Fatal neurotoxicity of arteether and artemether.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotoxicity in animals due to arteether and artemether.

Several artemisinin (qinghaosu) derivatives have been developed and are in use as antimalarial drugs but scant animal or human toxicity data are available. We noted a progressive syndrome of clinical neurological defects with cardio-respiratory collapse and death in 5/6 dogs dosed daily for 8 d with intramuscular arteether (AE) at 20 mg/kg/d in a pharmacokinetic study. Neurological findings included gait disturbances, loss of spinal reflexes, pain response reflexes and prominent loss of brain-stem and eye reflexes. Electrocardiography showed prolongation of the QT interval corrected for rate (QTc). Prominent neuropathic lesions were sharply limited to the pons and medulla. Neurological injury, graded by a pathologist 'blinded' to dose group, showed a dose-related region-specific injury which was most pronounced in the pons and medulla in all animals. Rats treated with AE and artemether (AM) at 12.5 to 50 mg/kg/d for 28 d confirmed clinical neurological abnormalities with high doses (> 25 mg/kg/d) after 6-14 d. Neuropathological examination of rat brain sections at 5 levels from the rostral cerebrum to the caudal medulla showed a dose-related pattern of injury characterized by hyalinized neuron cell bodies and loss of Nissl substance; changes congruent with those noted in dogs. No significant difference was noted in the extent, type, or distribution of lesions in the brains of rats treated with equivalent doses of AE or AM.(ABSTRACT TRUNCATED AT 250 WORDS)

Parvovirus enteritis in vaccinated juvenile bush dogs.

Parvovirus enteritis developed in 10 of 17 vaccinated juvenile bush dogs (Speothos venaticus) from 4 litters in a 5-month period. Nine dogs died. The first outbreak involved 6 of 9 bush dogs from 2 litters. Each had been vaccinated with a killed feline-origin parvovirus vaccine at 11 and 14 weeks of age. The 6 affected dogs became ill at 29 weeks of age and died. The second outbreak involved a litter of 6 bush dogs. Each had been vaccinated every 2 weeks starting at 5 weeks of age. Two were isolated from the colony at 16 weeks of age for treatment of foot sores. Three of the 4 nonisolated dogs developed parvovirus enteritis at 20 weeks of age; 2 died at 6 and 8 days, respectively, after onset of signs. The 3rd outbreak involved a litter of 2 bush dogs. Both had been vaccinated every 2 to 3 weeks, starting at 6 weeks of age. One of these dogs became ill at 17 weeks and died 13 days later. A litter of 6 maned wolves (Chrysocyon brachyurus) and a litter of 3 bush dogs were isolated from their parent colonies at 13 and 15 weeks of age, respectively. Each animal had been vaccinated weekly, beginning at 8 weeks of age, using an inactivated canine-origin parvovirus vaccine. None of the isolated animals developed the disease. Serologic testing during isolation did not reveal protective titers (greater than or equal to 1:80) against canine parvovirus in the bush dogs until they were 23 weeks old, whereas protective titers developed in the maned wolves when they were 14 to 18 weeks old. One hand-raised bush dog was vaccinated weekly, beginning at 8 weeks of age, and a protective titer developed by 21 weeks of age. It was concluded that the juvenile bush dogs went through a period during which maternal antibodies interfered with immunization, yet did not protect against the disease. When the pups were isolated from the colony during this period, then vaccinated repeatedly until protective titers developed, the disease was prevented.