Cardiovascular Proportionality of Modern Pigs : Are we breaking the allometric scaling laws ?

We have investigated, the proportionality of the cardiovascular system of modern pigs using allometric scaling laws. We found that heart weight scales with body weight in all examined weight categories (25-350 kg) and in animals under 100 kg also stroke volume and cardiac output scales with body weight, according to allometric scaling laws. But we found in heavier pigs (> 150 kg) that heart volumes like end-diastolic volume, stroke volume and cardiac output were relatively low regarding allometric scaling laws. The disproportionally low stroke volume was not the result of systolic dysfunction but of diastolic perturbations, likely as a result of an increased myocardial interstitial collagen content in conjunction with marked elevations in aortic blood pressure. These findings for one thing, underpin the growing concerns about intrinsic cardiovascular factors in modern pigs. In addition, we can conclude that heavy swine, as a result of these pathophysiological cardiovascular alterations, may be of value as an animal model to study cardiovascular disease, in particular heart failure preserved ejection fraction (HFpEF) in humans

The clinical spectrum of limb girdle muscular dystrophy. A survey in the Netherlands

A cross-sectional study was performed in the Netherlands to define the clinical characteristics of the various subtypes within the broad and heterogeneous entity of limb girdle muscular dystrophy (LGMD). An attempt was made to include all known cases of LGMD in the Netherlands. Out of the reported 200 patients, 105 who fulfilled strictly defined criteria were included. Forty-nine patients, mostly suffering from dystrophinopathies and facioscapulohumeral muscular dystrophy, appeared to be misdiagnosed. Thirty-four cases were sporadic, 42 patients came from autosomal recessive and 29 from autosomal dominant families. The estimated prevalence of LGMD in the Netherlands was at least 8.1 x 10-6. The clinical features of the autosomal recessive and sporadic cases were indistinguishable from those of the autosomal dominant patients, although half hypertrophy was seen more frequently, and the course of the disease was more severe in autosomal recessive and sporadic cases. The pectoralis, iliopsoas and gluteal muscles, hip adductors and hamstrings were the most affected muscles. Distal muscle involvement occurred late in the course of the disease. Facial weakness was a rare phenomenon. The severity of the clinical picture was correlated with a deteriorating lung function. All autosomal dominantly inherited cases showed a mild course, although in two families life-expectancy was reduced because of concomitant cardiac involvement

Heterogeneous clinical phenotypes and cerebral malformations reflected by rotatin cellular dynamics

Recessive mutations in RTTN, encoding the protein rotatin, were originally identified as cause of polymicrogyria, a cortical malformation. With time, a wide variety of other brain malformations has been ascribed to RTTN mutations, including primary microcephaly. Rotatin is a centrosomal protein possibly involved in centriolar elongation and ciliogenesis. However, the function of rotatin in brain development is largely unknown and the molecular disease mechanism underlying cortical malformations has not yet been elucidated. We performed both clinical and cell biological studies, aimed at clarifying rotatin function and pathogenesis. Review of the 23 published and five unpublished clinical cases and genomic mutations, including the effect of novel deep intronic pathogenic mutations on RTTN transcripts, allowed us to extrapolate the core phenotype, consisting of intellectual disability, short stature, microcephaly, lissencephaly, periventricular heterotopia, polymicrogyria and other malformations. We show that the severity of the phenotype is related to residual function of the protein, not only the level of mRNA expression. Skin fibroblasts from eight affected individuals were studied by high resolution immunomicroscopy and flow cytometry, in parallel with in vitro expression of RTTN in HEK293T cells. We demonstrate that rotatin regulates different phases of the cell cycle and is mislocalized in affected individuals. Mutant cells showed consistent and severe mitotic failure with centrosome amplification and multipolar spindle formation, leading to aneuploidy and apoptosis, which could relate to depletion of neuronal progenitors often observed in microcephaly. We confirmed the role of rotatin in functional and structural maintenance of primary cilia and determined that the protein localized not only to the basal body, but also to the axoneme, proving the functional interconnectivity between ciliogenesis and cell cycle progression. Proteomics analysis of both native and exogenous rotatin uncovered that rotatin interacts with the neuronal (non-muscle) myosin heavy chain subunits, motors of nucleokinesis during neuronal migration, and in human induced pluripotent stem cell-derived bipolar mature neurons rotatin localizes at the centrosome in the leading edge. This illustrates the role of rotatin in neuronal migration. These different functions of rotatin explain why RTTN mutations can lead to heterogeneous cerebral malformations, both related to proliferation and migration defects.Genetics of disease, diagnosis and treatmen

Diagnostic methods applied to analysis of an outbreak of equine influenza in a riding school in which vaccine failure occurred

An outbreak of equine influenza H3N8 in a riding school is described retrospectively with emphasis on diagnosis and putative vaccine failure. In March 1995 an outbreak of equine influenza occurred among 11 horses in a riding school, where most horses had received basic primary immunizations and several booster vaccinations against influenza. Six of the 11 diseased horses had received their last booster vaccination within 5 months of the outbreak. Nevertheless, the influenza infection spread rapidly and clinical manifestations were prominent with frequent, harsh, dry coughing often accompanied by high fever. Nasal swabs were taken from 11 diseased horses. Influenza A virus of the equine H3N8 (equi-2) subtype was isolated from five nasal swab extracts. Stored nasal swab extracts were also retrospectively investigated in two different enzyme immunoassays designed to detect the type-specific conserved nucleoprotein of influenza A viruses, and in a single-tube reverse transcription-PCR (RT-PCR) using a set of primers based on highly conserved regions of the matrix gene of influenza A viruses. Five nasal swab extracts were found positive in a DAS-ELISA and seven in the Directigen® Flu A (DFA) assay, respectively. Two nasal swab extracts from which virus was isolated did not give a positive result in the DAS-ELISA, and one of these also did not give a positive result in the DFA assay. Nine nasal swab extracts were found positive by RT-PCR. Moreover, all virus isolation and/or ELISA positive nasal swab extracts were confirmed by RT-PCR. Three nasal swab extracts were negative by virus isolation, PCR and ELISA. A significant rise in HI titre against influenza A/eq/Miami/63 (H3N8) virus was detected in seven of the nine paired sera available. In acute phase serum samples from 10 horses, SRH antibody levels varied widely. However, some horses with high, or at least putatively clinically protective SRH antibody levels, showed clinical signs and infection was confirmed. Antigenic analysis of two isolates showed that A/eq/Holland/1/95 (H3N8) and A/eq/Holland/2/95 (H3N8) cluster with the UK isolate Osgodsby/92, the Swedish isolate Borlänge/91 and some other European isolates, with H/2/95 identical in reactivity to Borlänge/91 and H/1/95 more similar in reactivity to Osgodsby/92 than H/2/95. Nucleotide and deduced amino-acid sequences showed large differences of both isolates as compared with Miami/63, Fontainebleau/79 and Kentucky/81, the influenza A H3N8 subtype strains incorporated in the vaccines used in this riding school. The role of antigenic drift in vaccine breakdown is discussed in the light of evidence for vaccine breakdown in the UK in 1989, Sweden in 1991 and in the USA since 1991

Diagnostic methods applied to analysis of an outbreak of equine influenza in a riding school in which vaccine failure occurred

An outbreak of equine influenza H3N8 in a riding school is described retrospectively with emphasis on diagnosis and putative vaccine failure. In March 1995 an outbreak of equine influenza occurred among 11 horses in a riding school, where most horses had received basic primary immunizations and several booster vaccinations against influenza. Six of the 11 diseased horses had received their last booster vaccination within 5 months of the outbreak. Nevertheless, the influenza infection spread rapidly and clinical manifestations were prominent with frequent, harsh, dry coughing often accompanied by high fever. Nasal swabs were taken from 11 diseased horses. Influenza A virus of the equine H3N8 (equi-2) subtype was isolated from five nasal swab extracts. Stored nasal swab extracts were also retrospectively investigated in two different enzyme immunoassays designed to detect the type-specific conserved nucleoprotein of influenza A viruses, and in a single-tube reverse transcription-PCR (RT-PCR) using a set of primers based on highly conserved regions of the matrix gene of influenza A viruses. Five nasal swab extracts were found positive in a DAS-ELISA and seven in the Directigen® Flu A (DFA) assay, respectively. Two nasal swab extracts from which virus was isolated did not give a positive result in the DAS-ELISA, and one of these also did not give a positive result in the DFA assay. Nine nasal swab extracts were found positive by RT-PCR. Moreover, all virus isolation and/or ELISA positive nasal swab extracts were confirmed by RT-PCR. Three nasal swab extracts were negative by virus isolation, PCR and ELISA. A significant rise in HI titre against influenza A/eq/Miami/63 (H3N8) virus was detected in seven of the nine paired sera available. In acute phase serum samples from 10 horses, SRH antibody levels varied widely. However, some horses with high, or at least putatively clinically protective SRH antibody levels, showed clinical signs and infection was confirmed. Antigenic analysis of two isolates showed that A/eq/Holland/1/95 (H3N8) and A/eq/Holland/2/95 (H3N8) cluster with the UK isolate Osgodsby/92, the Swedish isolate Borlänge/91 and some other European isolates, with H/2/95 identical in reactivity to Borlänge/91 and H/1/95 more similar in reactivity to Osgodsby/92 than H/2/95. Nucleotide and deduced amino-acid sequences showed large differences of both isolates as compared with Miami/63, Fontainebleau/79 and Kentucky/81, the influenza A H3N8 subtype strains incorporated in the vaccines used in this riding school. The role of antigenic drift in vaccine breakdown is discussed in the light of evidence for vaccine breakdown in the UK in 1989, Sweden in 1991 and in the USA since 1991

Thirty minutes transport causes small intestinal acidosis in pigs

Long duration (>10 hours) transport has been described as having either adverse or no effects on porcine health. However, the effect of short duration transport on porcine health is unknown. In the present paper, pigs fed ad lib turn (n = 6) were transported for 30 minutes, anaesthetised, instrumented, and cardiovascular and gastrointestinal parameters were measured. Non-transported pigs (n = 6) served as controls. No significant differences between groups were found concerning blood flow in the arteria mesenterica cranialis, heart rate, cardiac output, pulmonal blood pressure, haemoglobin content and haematocrit value. Systolic systemic blood pressure was higher (though not significant), and diastolic systemic blood pressure was significantly higher in the transported pigs than in the controls. Small intestinal pH was significantly lower in transported pigs than in control pigs. We conclude that a 30-minute transport of fed pigs results in small intestinal acidosis. As small intestinal acidosis predisposes to bacterial translocation, even short duration transport should be avoided when possibl

A review of porcine pathophysiology: a different approach to disease

Diseases are often thought to result from a single cause. Although this is sometimes the case, e.g. with a highly virulent infection such as Classical Swine Fever (CSF), more often clinical disease in swine herds results from multiple predisposing factors. This is especially true in modern intensive pig husbandry, in which the role of highly infectious diseases is limited to (nonetheless devastating) outbreaks. More important nowadays are diseases, although associated with an agent, without a clear pathogenesis. The emphasis in disease control thus far has been on treatment, eradication and prevention. This has been achieved by focusing attention on husbandry factors, such as climate, housing, hygiene, management, and nutrition. Although this approach has been successful for a number of diseases, several health problems are persistent. There are strong indications that in the latter, intrinsic animal factors are important. Successful handling of these problems requires knowledge of the (patho)physiology of the pig. In this article, several characteristics of pig physiology associated with the occurrence of disease are described. It appears that the modern (fattening) pig is exceptional among other animal species in that its cardiovascular system is mismatched to its body weight. It is argued that this particular disposition causes relatively minor disturbances to have major consequences in the pig. This concept of pig physiology is central to the understanding of the hitherto poorly understood pathogenesis of several diseases, such as oedema disease

A review of porcine pathophysiology: a different approach to disease

Diseases are often thought to result from a single cause. Although this is sometimes the case, e.g. with a highly virulent infection such as Classical Swine Fever (CSF), more often clinical disease in swine herds results from multiple predisposing factors. This is especially true in modern intensive pig husbandry, in which the role of highly infectious diseases is limited to (nonetheless devastating) outbreaks. More important nowadays are diseases, although associated with an agent, without a clear pathogenesis. The emphasis in disease control thus far has been on treatment, eradication and prevention. This has been achieved by focusing attention on husbandry factors, such as climate, housing, hygiene, management, and nutrition. Although this approach has been successful for a number of diseases, several health problems are persistent. There are strong indications that in the latter, intrinsic animal factors are important. Successful handling of these problems requires knowledge of the (patho)physiology of the pig. In this article, several characteristics of pig physiology associated with the occurrence of disease are described. It appears that the modern (fattening) pig is exceptional among other animal species in that its cardiovascular system is mismatched to its body weight. It is argued that this particular disposition causes relatively minor disturbances to have major consequences in the pig. This concept of pig physiology is central to the understanding of the hitherto poorly understood pathogenesis of several diseases, such as oedema disease