Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation - the clinical significance of having the mutation

Background

In Maine Coon (MC) cats the c.91G > C mutation in the gene MYBPC3, coding for cardiac myosin binding protein C (cMyBP-C), is associated with feline hypertrophic cardiomyopathy (fHCM). The mutation causes a substitution of an alanine for a proline at residue 31 (p.A31P) of cMyBP-C. The pattern of inheritance has been considered autosomal dominant based on a single pedigree. However, larger studies are needed to establish the significance of cats being heterozygous or homozygous for the mutation with respect to echocardiographic indices and the probability of developing fHCM. The objective of the present study was to establish the clinical significance of being homozygous or heterozygous for the p.A31P cMyBP-C mutation in young to middle-aged cats.

Methods

The cohort consisted of 332 MC cats, 282 cats < 4 years (85%). All cats were examined by 2-D and M-mode echocardiography. DNA was extracted from blood samples or buccal swabs and screened for the p.A31P cMyBP-C mutation in exon 3 of the gene, using polymerase chain reaction followed by DNA sequencing.

Results

The fHCM prevalence was 6.3% in the cohort. Eighteen cats were homozygous and 89 cats were heterozygous for the mutation. The odds ratio for having fHCM for homozygous cats was 21.6 (95% confidence interval 7.01-66.2) - when the group of equivocal cats was categorized as non-affected. Overall, 50% of the cats that were homozygous for the mutation had fHCM. p.A31P heterozygosity was not associated with a significant odds ratio for fHCM. In cats in the 4 to 6 years of age range a similar, non significant, odds ratio was seen in heterozygous cats. Only two cats over four years were homozygous and both were diagnosed with fHCM.

Conclusion

As there is no significant odds ratio associated with being heterozygous for the pA31P cMyBP-C mutation at this age, the mutation must have a very low penetrance in this group. From our data it would appear that most MC cats that develop fHCM due to the p.A31P mutation prior to the age of approximately 6 years do so because they are homozygous for this mutation.     

Developing new regulatory approaches to antimicrobial safety

Resistance to antimicrobial agents is of concern to public health officials worldwide. In industrialized countries, a significant source of antimicrobial-resistant food-borne infections in humans is the acquisition of resistant bacteria originating from animals. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. Recently the FDA published a guidance document titled 'Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern' (US Food and Drug Administration, Center for Veterinary Medicine, 2003). This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be used. The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high.     

Antimicrobial susceptibilities of Escherichia coli strains from a turkey operation

OBJECTIVE: To measure minimum inhibitory concentrations (MIC) of 17 antimicrobials for Escherichia coli isolates from a turkey operation and assess whether small samples provide precise estimates of geometric mean MIC. DESIGN: Prospective study. SAMPLE POPULATION: 105 clinical isolates from birds and 1,104 fecal isolates from 20 flocks (poults and finisher hens). PROCEDURE: A Mueller-Hinton broth dilution panel was used to measure MIC, and MIC of fecal and clinical isolates were compared. We drew random samples of 5,10, 15, 20, 25, 30, 35, 40, and 45 isolates from each finisher flock and between 100 and 105 isolates from 5, 7, 10, and 20 flocks. Antimicrobial usage was determined for enrolled flocks. RESULTS: Six of 12 poult and 18 of 20 finisher flocks had been treated with antimicrobials, often for respiratory illnesses consistent with colibacillosis. All birds received gentamicin at the hatchery. More fecal than clinical isolates were resistant to ampicillin; however, more clinical isolates were resistant to ciprofloxacin, gentamicin, and sulfamethoxazole. Precise estimates of geometric mean MIC for flocks were obtained when > or = 15 fecal isolates were obtained per flock and, for the operation, when 105 isolates were obtained from > or = 7 flocks. CONCLUSION AND CLINICAL RELEVANCE: Antimicrobial usage was common and may have contributed to the resistance patterns of isolates. With a modest allocation of laboratory resources, producers can monitor antimicrobial susceptibilities of clinical and fecal E coli to manage risks of antimicrobial usage and resistance.     

Biomass and phosphorus contents of some soil invertebrates

Data on the biomass, numbers and phosphorus content of three soil invertebrate families Enchytraeidae, Dorylaimidae and Elateridae are presented. The invertebrate specimens were from the Matador Canadian grassland site of the International Biological Programme. The soil invertebrates accounted for a small fraction of the total soil biomass but their role in P transformations seem to be relatively more important. P analyses indicated that of the total P in the invertebrate tissues less than half was present in organic combination and over half was measured in the inorganic form.     

The degradation of 14C-labelled phosphatidyl choline in soil

When phosphatidyl [N-methyl-¹⁴CO]choline or phosphatidyl choline di[l-¹⁴C]palmitoyl were incubated in a low phosphorus status soil there was an early and rapid release of CO₂ and a concurrent increase in NaHCO₃-extractable inorganic phosphorus, indicating mineralization of the added organic phosphorus. Mineraiization slowed dramatically and by 20 days only 50% of the carbon from the molecule was accounted for as microbial biomass or respiration. The rates of release of ¹⁴CO₂ from the two labelled substrates indicated that ¹⁴CO₂ measured as respiration initially arose more swiftly from the carbon portion of the molecules with easiest access to enzymic degradation.     

Producer quality assurance programs.

Essentially all animal commodity organizations have established quality assurance programs designed to ensure food safety and quality. Most of these programs were originally implemented to address problems with veterinary drug residues. Many of the current programs have or plan to include food safety critical control points with specific guidelines on how to control or reduce pathogen load. The continued focus placed on food safety by today's consumer demands that American producers ensure that their commodities are wholesome, safe, and of high quality in order to remain competitive in the global marketplace. Veterinarians should recognize that it is important to encourage food animal producers to participate in quality assurance programs for their clients' economic health and for food safety and protection of public health. Commodities certified as being produced under good production practices or by producers certified as following a recognized and validated quality assurance program often bring a premium price. Also, some slaughter establishments are beginning to require producers to be certified as practicing under a recognized quality assurance program before animals are accepted for processing. This practice is being driven partially by the demands placed on slaughter establishments by the US Department of Agriculture's implementation of the Pathogen Reduction, Hazard Analysis and Critical Control Point Systems regulation. Regardless of why producer trade association quality assurance programs have come into existence, veterinarians should promote the programs as an excellent mechanism to help ensure everyone's goal of a safe, wholesome food supply.