European view toward incorporating adverse events into package inserts.

The information contained in package inserts varies from country to country in Europe, although other regulatory aspects of data presentation are quite similar. West Germany's Drug Law of 1976 requires 11 items to be included in the package insert for both patient and health professional: name/address of manufacturer; drug name; active constituents; indications; contraindications; side effects; drug interactions; dosage instructions; method and duration of application; statement that drug should not be used after expiration date; and statement that drug should be kept out of reach of children. All information must be submitted to the Health Office at the time of application or the applicant is liable for criminal prosecution. Documentation of side effects must be complete, although no special form is required. Similarly, causality assessment needs to be made even though specific algorithms are not required. Proposed amendments to the Drug Law will include additional information to physicians concerning the overdose instructions, pharmacological properties, and bioavailability of the drug. Registration procedures are the same throughout Europe and are called Summary of Products Characteristics. Assessment reports are also required for each new chemical entity in the European Community.     

Repeated measurements of mite and pet allergen levels in house dust over a time period of 8 years

BACKGROUND: Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. OBJECTIVE: We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. RESULTS: Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. CONCLUSION: Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended.     

Ethische Aspekte der ästhetischen Medizin

The article examines the question whether and – if – under which conditions physicians should perform purely esthetic interventions. Starting point of the considerations is the special character of the medical profession and the necessity of the anticipated confidence in the system of medicine. The medical measures for aesthetic improvement are systematized. Medical measures to increase the wanted, positively felt attention of others are not compellingly required according to the medical ethic. Nevertheless they do not offend the ethos if high quality standards are insured: The measures must be presumably helpful for the patient; a thorough informed consent and avoidance of damage must be insured. Esthetic measures, in particular operations which are totally cosmetic, should be limited strictly if performed with children and adolescents. Nevertheless convincing arguments support medical-esthetic measures with children and adolescents to avoid stigmatization.     

Ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase A2 into mammalian motor nerve terminals

A mutant form of ammodytoxin A, a neurotoxic phospholipase A₂ from the venom of the long nosed viper Vipera ammodytes ammodytes, was prepared by site-directed mutagenesis, conjugated to a nanogold particle and inoculated into the antero-lateral aspect of one hind limb of female mice. Eight hours later the mice were killed, the soleus muscles of both ipsi- and contra-lateral hind limbs were removed, exposed to a silver enhancing medium and then prepared for transmission electron microscopy. Silver-enhanced particles were subsequently found concentrated in the peri-synaptic area, particularly within the synaptic gutter and the deep synaptic folds, and in many cases had been taken up into the cytoplasm of the terminal boutons of the motor axon. The results suggest that the presynaptic neurotoxicity of snake venom phospholipases A₂ involves several components of the neuromuscular apparatus, including intracellular organelles of the motor nerve terminal.     

The use of microfluorometry to study DNA in nasopharyngeal carcinomas: a possible prognostic tool?

A microfluorometric method was used to determine the nuclear DNA content in the nasopharyngeal carcinomas (NPC) of 25 patients treated before 1983. Eleven patients are still alive with no evidence of disease (NED), while the rest died of their disease (DOD). All of the patients received a cycle of radiotherapy, while some also received chemotherapy or neck dissections. The neoplastic cells studied were taken from the original biopsy blocks, deparaffinized, isolated by enzymatic treatment and mechanical fragmentation, and then Feulgen-stained. The cytofluorometric measurement was carried out by a microphotometer equipped for fluorescence excitation and connected to a computer. This method allowed us to construct a histogram of the DNA content in the neoplastic cells. Different neoplastic classes were identified and represent the heteroclonality of the tumor, which can be expressed by the heteroclonality index (HCT). From the collected data it appears that the NED patients all had a low HTC (less than 1) and only 7 of the DOD patients had low HTCs (less than 1). Six of the DOD patients with a low HTC were in advanced stages of their tumor at the time of diagnosis, while the remaining patient did not complete his treatment. Our results show that the DNA analysis of the NPC cell population may offer a useful tool in predicting the biological behavior of this tumor and also improving its treatment.