Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

Canada goose (Branta canadensis) droppings as a potential source of pathogenic bacteria.

Canada goose droppings, collected in parks to which the public had access, were screened for a range of bacteria that could be pathogenic in man. Droppings of Canada geese, and other waterfowl, did contain such bacteria, including some that are well-known causes of illness in man. These bacteria, plus a species of Salmonella that was experimentally inoculated into droppings, were shown to survive and multiply in the droppings for up to one month after their deposition by geese. Canada geese ranged further from water than other waterfowl species and thus distributed their droppings over a larger area of park grassland. This more widespread distribution of their droppings leads Canada geese to pose a greater potential health risk than other waterfowl studied here, but variations in human responses to challenge with bacteria, and variations in human and waterfowl behaviour in public parks, renders quantification of this risk impossible.

Specific assays for bacteria using phage mediated release of adenylate kinase.

A sensitive and rapid assay method for the specific detection of bacteria was developed using Escherichia coli and Salmonella newport as the test organisms. Bacteriophages were used to provide specific lysis of the bacteria and then the release of cell contents was measured by ATP bioluminescence. Increased sensitivity was obtained by focusing on the bacteria's adenylate kinase (AK) as the cell marker instead of ATP as conventionally used. Fewer than 10(3) E. coli cells could be readily detected in less than 1 h. Salmonella newport assays, although as sensitive, were slower and took up to 2 h. The effects of the culture medium, the phage, and the presence of non-specific bacteria were examined.

Dosimetric characteristics of an improved radiochromic film.

Recently, a new model of radiochromic film has been developed for medical applications to provide a higher sensitivity and better uniformity of response than existing models (i.e., MD-55). Dosimetric characteristics including sensitivity, linearity, reproducibility, uniformity, and dependence on energy and time have been studied experimentally. The characteristics of the new films were compared with those of model MD-55. For these investigations, the two films were exposed to ionizing radiation in the dose range from 1-72 Gy, using gamma-rays from a 60Co teletherapy unit and 6- and 18-MV x rays from a linear accelerator. The response of the exposed film was measured with a helium-neon laser densitometer. The results indicated that the sensitivity of the improved film was about 40% greater than that of MD-55 film. Moreover, the response of the improved film was found to be uniform within 4% only in one direction of the film. The orthogonal direction indicated a nonuniformity of up to 15%, similar to that of model MD-55. Less than 5% energy dependence in the megavoltage photon range was observed for the new film. Complete dosimetric characteristics of the new film are presented.

Use of isoelectric focusing to define major histocompatibility complex class I polymorphism in goats.

We have used biochemical methods to extend and improve serological class I typing using a panel of 77 Swiss goats of the Saanen breed, comprising dam-offspring combinations from six half-sib sire families and several unrelated animals. Of these animals class I molecules were precipitated from cell lysates with the mAb B1.1G6 and HC10. Immunoprecipitates were analysed by SDS-PAGE and 1D-IEF. There was a good agreement between class I serological types and IEF banding patterns. We have identified three new class I specificities and subdivided the Be17 specificity. IEF has enabled us to make planned immunizations to produce antisera to the new specificities. New evidence for the expression of a second class I locus product in the Be7 haplotype has been found.

Involvement of major histocompatibility complex class I compatibility between dam and calf in the aetiology of bovine retained placenta.

The possibility was examined that in cattle compatibility of major histocompatibility complex (MHC) products between dam and calf might negatively influence the placental maturation and expulsion, and therefore increase the risk of retained placenta in healthy, normally calving cattle. Fifteen combinations of a single dam and two offspring were selected; the placenta of the first offspring was normally expelled (control) and the placenta of the second one was retained (case). The MHC class I and class II antigens of the animals were typed by immunoprecipitation and by one-dimensional isoelectric focusing (1D-IEF). Compatibility or incompatibility of class I or class II antigens was established by comparison of the IEF banding patterns of dam and calves. Analysis revealed that MHC class I compatibility between dam and calf increased the risk of retained placenta. In this study, the effect of class II compatibility was not significant, nor was the effect of the interaction of class I and class II. In a subsequent, additional sample the experimental design was extended: induction of tolerance against non-inherited maternal antigens (NIMA) might be implicated in the occurrence of the disorder within the group of class I incompatible cases. In three out of the five class I incompatible retained placenta cases, the banding pattern of the incompatible haplotype of the calf was identical to that of the haplotype of the granddam that was not inherited by the dam (NIMA). Notably, within the nine class I incompatible controls, there were none in which the offspring shared a paternal class I type with the granddam. This might suggest a tolerance-inducing effect of NIMA in cattle in relation to retained placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

An appraisal of bioassay methods for the detection of mycotoxins--a review.

The literature on bioassay methods for mycotoxin detection has been reviewed. An outline of the range of bioassay methods is given and the role of cytotoxicity tests in particular has been emphasized.

Myxomatosis in farmland rabbit populations in England and Wales.

The overall pattern and consequences of myxomatosis in wild rabbit populations were studied at three farmland sites in lowland southern England and upland central Wales between 1971 and 1978. When results from all years were combined, the disease showed a clear two-peaked annual cycle, with a main autumn peak between August and January, and a subsidiary spring peak during February to April. Rabbit fleas, the main vectors of myxomatosis in Britain, were present on full-grown rabbits in sufficient numbers for transmission to occur throughout the year, but the observed seasonal pattern of the disease appeared to be influenced by seasonal mass movements of these fleas. However other factors were also important including the timing and success of the main rabbit breeding season, the proportion of rabbits which had recovered from the disease and the timing and extent of autumn rabbit mortality from other causes. Significantly more males than females, and more adults and immatures than juveniles, were observed to be infected by myxomatosis. Only 25-27% of the total populations were seen to be infected during outbreaks. Using two independent methods of calculation, it was estimated that between 47 and 69% of infected rabbits died from the disease (much lower than the expected 90-95% for fully susceptible rabbits with the partly attenuated virus strains that predominated). Thus it was estimated that 12-19% of the total rabbit populations were known to have died directly or indirectly from myxomatosis. Although the effects of myxomatosis were much less than during the 1950s and 1960s, it continued to be an important mortality factor. It may still have a regulatory effect on rabbit numbers, with autumn/winter peaks of disease reducing the numbers of rabbits present at the start of the breeding season.

Characterization of class I bovine lymphocyte antigens (BoLA) by one-dimensional isoelectrofocusing.

BoLA class I antigens were characterized in a group of British and Dutch Friesian cattle by one-dimensional isoelectric focusing (1D-IEF) and the results compared with serology using alloantisera and microcytotoxicity. For IEF analysis, non-stimulated peripheral blood mononuclear cells (PBM) were metabolically labelled with 35S methionine, detergent lysates were prepared and MHC molecules precipitated with the monoclonal antibodies (mAbs) W6/32 or B1.1G6. Staphylococcus protein A precipitated antigens were separated on a vertical slab gel under denaturing conditions. The banding patterns seen for the W6/32 precipitated molecules obtained by 1D-IEF were compared with the serological specificities. Characteristic banding patterns were observed for most serological specificities as well as workshop undefined haplotypes. These patterns were seen both in families and the outbred population. In families IEF haplotypes segregated with serotypes. Additional MHC class I products were suggested by variable banding patterns for different w10 haplotypes and when using the different mAbs. A pulse chase experiment with a w12 animal also suggested more than one expressed product. The w2 and w5 specificities were not precipitated by either W6/32 or B1.1G6 and w6.2 and w6.4 were precipitated by W6/32 but not by B1.1G6. These results show that 1D-IEF is useful for BoLA typing. For the characterization of class I antigens, however, much depends on the mAbs used.

Changes in the virulence of myxoma virus strains in Britain.

National surveys of the virulence of field strains of myxoma virus were carried out in 1975 (128 virus strains) and in 1981 (123 strains), using the virulence testing method employed in a similar survey in 1962. Results showed that the virulence of field strains had increased between 1962 and 1975, and again between 1975 and 1981. The increases in virulence are thought to be a result of the development of resistance to myxomatosis in wild rabbit populations. The effects of the changes in virulence and resistance are discussed.

The development of genetic resistance to myxomatosis in wild rabbits in Britain.

The presence of genetic resistance to myxomatosis in a sample of wild rabbits from one area in England was reported in 1977. Rabbits from three other areas in Great Britain have been tested subsequently, and all cases showed similar resistance to a moderately virulent strain of myxoma virus. Rabbits from one area also showed a significant degree of resistance to a fully virulent strain of virus. It is concluded that genetic resistance to myxomatosis is widespread in wild rabbit populations in Britain. The implications of the results are discussed in relation to the co-evolution of the disease and its host.

The effects of temperature and pH variations on plaque production by different virulence types of myxoma virus.

Eight 'strains' of myxoma virus, spanning the complete spectrum of virulence, were tested for ability to produce plaques on rabbit kidney cells at varying temperatures and pH values. A positive correlation was found between virulence in rabbits and ability to produce plaques at supra-optimal temperature and at low pH.

Methods of isoelectric focusing.

The method of isoelectric focusing has been avoided by many workers because of expense, technical difficulty, and problems of interpretation. Inexpensive, easy, and interpretable results are possible using equipment and reagents commonly available. Methods which allow these results are presented and explained.

Innate resistance to myxomatosis in wild rabbits in England.

Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times.In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed.The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level.