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Serum antibodies against measles were measured in the Dutch general population and in municipalities with low vaccine coverage, where religious groups that refuse vaccination are clustered sociogeographically. The results suggest that wild measles virus may still circulate in municipalities with low vaccine coverage; the circulation in the general population seems to have decreased significantly right after the introduction of mass vaccination. The overall prevalence in the general population was high (95.7%, 95% confidence limits 95.3-96.2%); the seroprevalence in the age groups offered two vaccinations (91.7%, 95% confidence limits 89.4-94.0%) was lower than the level believed to be necessary for the elimination of measles. Protective levels of maternal antibodies in newborns have waned several months before the first vaccination is scheduled.

A two-dose mass vaccination programme with a combined vaccine against measles, mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the selective schoolgirl vaccination strategy introduced in 1974. To obtain insight into the effect of mass vaccination and the population's immunity, the antibody levels against rubella were studied in the general Dutch population and in religious groups refusing vaccination. In the national sample, we observed a high prevalence (96.5%) for rubella antibodies in vaccinated cohorts as well as in the older unvaccinated cohorts. No indications of rapidly waning immunity after vaccination were found. There are indications of low virus circulation in the last few years. The very high seroprevalence in women at childbearing age is consistent with the few reported cases of congenital rubella syndrome (CRS) at present. However, individuals in the age group of 1-9 years who are not vaccinated for religious or other reasons have a considerably lower seroprevalence and thus there is a potential risk of a CRS outbreak in the future.

We assessed the tetanus immunity of the general Dutch population and of religious groups refusing vaccination by means of population-based study to evaluate the effect of tetanus vaccination. More than 95% of those born after the introduction of routine vaccination had tetanus antitoxin levels above the minimum protective level. After the sixth vaccination, a fall in tetanus antitoxin levels occurred. Nevertheless, immunisation in accordance with the routine programme most likely induces protection for much longer than two decades. Not only many members of religious groups who refuse vaccination, but also many adults born before the introduction of vaccination lack tetanus immunity. These cohorts might benefit most from (re)vaccination.

Self-management plans are considered today an essential component of the management of asthma. The objective of the present study was (a) to explore patients' present practical knowledge of self-treatment of asthma, and (b) to provide an assessment of the effect of an educational program on this knowledge and self-treatment behaviour. Twenty four adults with asthma from the outpatient clinic of the Department of Pulmonary Medicine participated in a self-management program. They were provided with explanations on the symptoms and precipitating factors of their asthma, on its treatment with medication and their side-effects, and with personal written guidelines for self-adjustment of their medication. Prior to the program their practical knowledge of adequate self-treatment was investigated using a hypothetical scenario of a slow-onset asthma exacerbation. The effectiveness of the teaching and training program was evaluated by the change in knowledge prior to and 5 months after the program and self-reported behaviour of the participants at follow-up. (a) More than 60% of the patients lacked practical knowledge of self-treatment of a slow-onset exacerbation of asthma. (b) The educational program resulted in a significant increase (47%) of this knowledge. (c) Actual self-treatment behaviour, as recorded by the patients 5 months after completing the educational program, was adequate in only two of ten patients, who experienced an exacerbation during the study period. Many adults with asthma are deficient in practical knowledge of self-treatment of a slow-onset exacerbation. This knowledge was significantly augmented by an educational program. Nevertheless actual self-treatment behaviour at follow-up was inadequate in the majority of patients.

Molecular recognition, site-directed mutagenesis, and molecular modeling are combined to describe hydrogen bonds important for formation and catalysis of the Aspergillus niger glucomylase-isomaltose complex. This analysis of the energetics of the transition-state complex identified OH-4', -6', and -4 as critical for isomaltose hydrolysis. Side-chains hydrogen bonded to isomaltose OH-4 (reducing end unit, i.e. at glucoamylase binding subsite 2) induced substrate conformation adjustment to optimize binding energy contributed by charged hydrogen bonds to OH-4' and -6' at the non-reducing unit (i.e. at subsite 1). These interactions were evident in the modeled complex of glucoamylase and isomaltose in the preferred trans-gauche conformation. Kinetic analysis demonstrated reductions in kcat of 10(3) to 10(5)-fold for the corresponding deoxy- and O-methyl analogs of isomaltose. Analysis of two mutants at the level of subsite 2, Glu 180-->Gln and Asp 309-->Glu, showed the binding energy for the enzyme-transition state complex, delta delta G, contributed by OH-3 and -4 to be 6-7 kJ mol-1 weaker than with wild-type enzyme. Unexpectedly, however, substitution of isomaltose OH-4' and -6' (at subsite 1) resulted in 10 to 12 kJ mol-1 lower delta delta G++ for both the mutants. Mutation at subsite 2, therefore, strongly perturbed distant transition-state stabilizing interactions. This was confirmed with 4'- and 6'-deoxy analogs of the conformationally biased methyl 6-R-C-methyl-alpha-isomaltoside, readily adopting trans-gauche conformation, that exhibit full delta delta G++ 18 to 20 kJ mol-1 for both mutants and wild-typ-. Glucoamylase, during catalysis, thus seems to induce a change from the predominant solution gauche-gauche conformer to trans-gauche isomaltose. This leads to enhanced binding at subsite 1 in the enzyme transition-state complex.