False hyperchloraemia in a dog secondary to ingestion of horse feed supplemented with potassium bromide.

BACKGROUND: A dog was presented for acute abdominal distension after inadvertent access to a large amount of dry dog food and possibly horse feed consisting of chaff, pony cubes and vitamin, mineral and yeast supplements. RESULTS: A marked hyperchloraemia and decreased anion gap on blood electrolyte analysis prompted a review of the patient's history for potential ingestion of bromide. It was revealed that the horse feed was supplemented with potassium bromide. The serum bromide level was 23.6 mmol/L. The dog recovered uneventfully. CONCLUSION: This case report highlights the importance of knowing common interferents of chemical analysis techniques.

Aplysia gigantea toxicosis in 72 dogs in Western Australia.

OBJECTIVES: This study aimed to: (1) confirm a temporal association between exposure to the sea hare Aplysia gigantea and the development of a neurotoxicosis in dogs and (2) further characterise the clinical signs, treatment and outcomes in dogs with this suspected toxicosis. METHODS: The medical records from four veterinary practices within the Geraldton region of Western Australia were searched for dogs that had been exposed to A. gigantea and subsequently presented to a veterinarian during the period of January 2001 to March 2011. Signalment, exposure history, clinical signs, treatment and outcome were recorded. RESULTS: In total, 72 dogs met the inclusion criteria. Clinical signs included ptyalism, emesis, ataxia, hyperaesthesia, tremors, muscle fasciculations, seizures, nystagmus and respiratory distress; 30 dogs did not have abnormal clinical signs at presentation; 69 dogs were presented during January to April. Treatment included gastrointestinal and dermal decontamination, and supportive management of seizures, tremors and muscle fasciculations. Of the 72 dogs, 65 survived to discharge, 4 died and 3 were euthanased. Information from subsequent examinations was available for 57 dogs and no long-term complications were reported. CONCLUSIONS: Exposure to A. gigantea was temporally associated with the development of neuroexcitatory clinical signs in dogs. Gastrointestinal and respiratory signs also occurred in some dogs. Dogs with suspected toxicosis were presented mostly in the months of January to April. The proportion of dogs that died or were euthanased because of worsening clinical signs was approximately 10%.

A linkage survey of 20 dominant retinitis pigmentosa families: frequencies of the nine known loci and evidence for further heterogeneity.

Autosomal dominant retinitis pigmentosa (ADRP) is caused by mutations in two known genes, rhodopsin and peripherin/Rds, and seven loci identified only by linkage analysis. Rhodopsin and peripherin/Rds have been estimated to account for 20-31% and less than 5% of ADRP, respectively. No estimate of frequency has previously been possible for the remaining loci, since these can only be implicated when families are large enough for linkage analysis. We have carried out such analyses on 20 unrelated pedigrees with 11 or more meioses. Frequency estimates based on such a small sample provide only broad approximations, while the above estimations are based on mutation detection in much larger clinic based patient series. However, when markers are informative, linkage analysis cannot fail to detect disease causation at a locus, whereas mutation detection techniques might miss some mutations. Also diagnosing dominant RP from a family history taken in a genetic clinic may not be reliable. It is therefore interesting that 10 (50%) of the families tested have rhodopsin-RP, suggesting that, in large clearly dominant RP pedigrees, rhodopsin may account for a higher proportion of disease than had previously been suspected. Four (20%) map to chromosome 19q, implying that this is the second most common ADRP locus. One maps to chromosome 7p, one to 17p, and one to 17q, while none maps to 1cen, peripherin/Rds, 8q, or 7q. Three give exclusion of all of these loci, showing that while the majority of dominant RP maps to the known loci, a small proportion derives from loci yet to be identified.

Variation at the lipoprotein lipase and apolipoprotein AI-CIII gene loci are associated with fasting lipid and lipoprotein traits in a population sample from Iceland: interaction between genotype, gender, and smoking status.

The effects of polymorphisms in the lipoprotein lipase (LPL) gene (HindIII and S447X) and in the apolipoprotein (apo) AI-CIII gene cluster (G75A and C1100T) on levels of fasting plasma triglycerides, apoCIII, high density lipoprotein cholesterol (HDL-C), and apoAI were examined in 315 healthy men and women from Iceland. Non-smoking and smoking men and women were examined separately because of the strong effects of smoking status and gender on lipoproteins. For the LPL gene, there were no significant associations between plasma traits and genotypes of the S447X polymorphism, but the LPL-HindIII polymorphism was associated with significant effects on levels of all traits, with the effect of genotype on triglycerides and apoAI being modulated by smoking status, (genotype x smoking interaction, P < .02). The H- allele was generally associated with slightly lower levels of apoCIII, with a lowering effect on triglycerides only in smokers and with a raising effect on ApoAI in non-smoking and smoking men and in non-smoking women. For the apoCIII C1100T polymorphism, smoking and non-smoking men with one or more T alleles had levels of triglycerides roughly 10% higher than those with only the C allele; in contrast, the women with the T allele had lower levels of triglycerides (15.7% lower in non-smokers, P = .04; gender x genotype interaction, P = .02). In males and females and in smokers and non-smokers, the T allele was associated with levels of apoCIII that were 9-20% higher than those with only the C allele (P = .004 overall). In the non-smoking men, nonlinear additive effects were observed with combinations of genotypes at the LPL and apoAI-CIII loci, with the HDL-C and apoAI raising effect associated with the A75 allele and H- allele seen only in those men with both alleles, and the apoCIII raising effect associated with the H+ and T alleles seen only in those with both alleles. Thus, variations at both of the LPL and apoAI-apoCIII loci influence levels of triglycerides, apoCIII, HDL-C, and apoAI, but these effects are strongly modulated by smoking and are different between men and women. The mechanisms for these interactions between smoking or gender and genes are unknown, but future studies should take such interactions into account.

Analysis of a human gene homologous to rat ventral prostate.1 protein.

We report on the analysis of a human gene homologous to the rat ventral prostate.1 protein (RVP.1), which is transcriptionally induced in the regressing rat prostate after castration. EST database searching and Northern blotting reveal that this is one of at least four different members of a gene family in the human genome that produce transcripts of 3.4, 2.4, 1.9, and 1.2 kb, expressed in a wide range of tissues. Three other members of this gene family have already been mapped to chromosomes 7q, 17p, and 22q and reported either as anonymous ESTs or as full-length clones. We have now characterized a fourth member (assigned the gene now characterized a fourth member (assigned the gene name C7orf1 by GDB) and localized it also to chromosome 7q. C7orf1 is almost identical over much of its length to the reported ORF of RVP.1 while the other family members are more divergent from RVP.1. The genomic sequence of C7orf1 is intron-less, is spanned by a CpG low-methylation island, and has two noncoding, nonpolymorphic STR regions immediately adjacent to the open reading frame, one 5' and one 3'. The presence of a NotI restriction site in the coding sequence results in a deficiency in the IMAGE cDNA libraries, as a result of which the 3' end of the gene is not in the EST databases. The putative 220-amino-acid protein shows 89% identity to the amino terminus of rat RVP.1. Like rat RVP.1, it has four hydrophobic potential membrane-spanning regions, but it lacks 60 amino acid residues at its carboxyl terminus relative to rat RVP.1. Nevertheless, gene-specific primers from this transcript amplified a product in human cDNAs from several different tissues; its size corresponds to the 1.2-kb transcript seen on a Northern blot, and identical ESTs from several different tissues exist in the databases. It therefore seems likely that C7orf1 is the closest human homologue of rat RVP.1.

Interaction of the lipoprotein lipase asparagine 291-->serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults.

A mutation in the lipoprotein lipase (LPL) gene, resulting in the substitution of asparagine by serine at residue 291 (LPL-S291), was found to occur in young survivors of a myocardial infarction from Sweden, combined hyperlipidemic subjects from the United Kingdom, and type III hyperlipidemic subjects from Germany at allelic carrier frequencies no different from those found in companion healthy control subjects (3.63 vs. 3.37; 1.85 vs. 1.60; and 2.00 vs. 1.56%, respectively). In a group of 620 healthy middle-aged men from the United Kingdom with baseline and three subsequent annual lipid measurements, mean plasma triacylglycerol (TG), (but not plasma cholesterol) concentrations in carriers of the mutation were significantly elevated over non-carriers (1.95 vs. 1.61 mmol/l, P = 0.05, and 5.83 vs. 5.65 mmol/l, P = 0.29, respectively). When these healthy control subjects were divided according to tertiles of body mass index (BMI), as expected, non-carriers whose BMI was in the upper two tertiles (BMI > or = 25.0 kg/m2) had higher plasma TG concentrations than those in the lowest tertile (1.90 vs. 1.54 mmol/l), but this difference was much greater in LPL-S291 carriers (2.33 vs. 1.36 mmol/l, P = 0.01, BMI x genotype interaction, P = 0.02). To confirm this effect, a second group of 319 healthy subjects from the United Kingdom was screened for LPL-S291. The allelic frequency of the mutation was found to be 1.88% and the effect on plasma lipid concentrations was very similar to that observed in the first control group (plasma TG, 2.31 vs. 1.27 mmol/l, P < 0.001 for LPL-S291 carriers vs. non-carriers, respectively). As before, those carriers whose BMI was in the top two tertiles for this sample (BMI > or = 23.3 kg/m2) had higher plasma TG concentrations than non-carriers (2.31 vs. 1.42 mmol/l). Thus, the LPL-S291 variant may predispose individuals to elevated plasma TG concentrations under conditions such as increased BMI.

The genetic determinants of plasma cholesterol and response to diet.

In general, risk factors for multifactorial disorders such as atherosclerosis and hyperlipidaemia show a continuous distribution in the population, and this is the result of both interaction between genetic variation at genetic loci, and genetic and environmental interaction. Therefore, the investigation of the genetics of intermediate phenotypes such as levels of plasma lipid traits is likely to be particularly informative. Once the genes involved in determining the levels of these phenotypes have been identified, it should be possible to use the information to obtain a better understanding of the way these genetic variations determine the clinical end points. In the population it will be possible to identify a number of polygenes that are having a small effect on determining the trait, but for a particular individual, or the relatives of that individual, only a subset of all these polygenes will determine the level of the trait and therefore the risk of developing the disorder. In general, mutations with a large effect on the trait are rare in the population, By contrast, polymorphisms with a small effect on the trait may be common, such as is found with the effect of the apoE alleles and variation at the apoB gene locus on lipid levels. In the field of hyperlipidaemia and atherosclerosis research, molecular techniques have already given a great deal of information on how specific sequence variations in some of the candidate genes are involved in determining levels of plasma apoproteins, lipoproteins and lipids. As more mutations and sequence variations are identified, this will not only aid our understanding of the underlying pathology, but should be useful for identifying individuals who are at risk of developing atherosclerosis because of their particular genotype or combination of genotypes.

A YAC contig spanning the dominant retinitis pigmentosa locus (RP9) on chromosome 7p.

The dominant retinitis pigmentosa locus RP9 has previously been localized to 7p13-p15, in the interval D7S526-D7S484. We now report refinement of the locus to the interval D7S795-D7S484 and a YAC contig of approximately 4.8 Mb spanning this region and extending both distally and proximally from it. The contig was constructed by STS content mapping and physically orders 29 STSs in 28 YAC clones. The order of polymorphic markers in the contig is consistent with a genetic map that has been assembled using haplotype data from the CEPH pedigrees. This contig will provide a primary resource for the construction of a transcriptional map of this region and for the identification of the defective gene causing this form of adRP.

Common variation in the gene for apolipoprotein B modulates postprandial lipoprotein metabolism: a hypothesis generating study.

We have carried out a pilot study to examine the influence on postprandial lipid and lipoprotein metabolism of common genetic variation in the gene coding for apolipoprotein (apo) B, in a previously described group of 30 individuals who had survived a myocardial infarction (MI) before the age of 45 (normo (NTG)- and hypertriglyceridaemic (HTG) patients) and 11 age-matched healthy individuals. Postprandial lipid or lipoprotein levels were examined by genotypes in the three groups separately and after adjustment for fasting triglycerides (TG) in the whole group combined. For the signal peptide polymorphism in the apo B gene, individuals with one or more SP-24 alleles had a 38% smaller mean area under curve (AUC) (P = 0.06) for postprandial large chylomicron remnants and a 29% smaller mean AUC (P = 0.01) for large very low density lipoproteins (VLDLs) compared to individuals homozygous for the wild type SP-27 allele. Previously in this patient group, small chylomicron remnants (apo B-48 levels in the Sf 20-60 range) were found to relate significantly and positively to progression of coronary atherosclerosis suggesting that these lipoproteins are implicated in progression of atherosclerosis. For the apo B Val591-Ala polymorphism (Ag a1/d), individuals homozygous for the V591 allele had a 33% greater AUC for Sf 20-60 postprandial triglycerides (P = 0.006), with higher postprandial levels of both apo B-48- and apo B-100-containing lipoproteins in this fraction. This pilot study gives insight into the mechanisms of the previously reported associations between polymorphisms in the apo B gene and fasting plasma lipids and lipoproteins.

Associations of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses.

Association studies were carried out in a sample of 86 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) AI-CIII-AIV gene cluster on among-individual differences in plasma lipid and lipoprotein traits, the five high density lipoprotein (HDL) subclasses (2b to 3c), lipoprotein lipase (LPL) activity and presence and progression of atherosclerosis. Individuals were genotyped for four polymorphisms; 5'apoAI (G/A-75), 3'apoAI (PstI; P +/-), apoCIII (C/T1100) and apoCIII (PvuII; V +/-), using PCR-based techniques. Allele frequencies were similar in healthy individuals and patients (frequencies of alleles in combined population: 5'apoAI-A-75 = 0.14, 3'apoAI-P- = 0.05, apoCIII-T1100 = 0.27 and apoCIII-V- = 0.18). In the healthy individuals, levels of low density lipoprotein (LDL) triglycerides were significantly associated with genotypes of the apoCIII-PvuII polymorphism (p = 0.02), but no other associations were found between lipids or HDL subclasses and single polymorphisms in the apoAI-CIII-AIV gene cluster. Levels of triglycerides and very low density lipoprotein (VLDL) triglycerides were significantly higher in the presence of the haplotype defined by the presence of apoCIII-T1100 and common alleles of the other three polymorphisms, explaining 5.8% and 7.8% (p = 0.03 and 0.01), respectively, of sample variance. In the patients, no associations were found between lipids or HDL subclasses and variation at the apoAI-CIII-AIV gene cluster. Associations were also examined between levels of HDL subclasses and variation at the apoE (common isoforms), apoB (signal peptide and XbaI polymorphisms) and lipoprotein lipase (PvuII, HindIII and Serine447/Stop polymorphisms) gene loci. In the patient group only, levels of protein in HDL2b, HDL2a and HDL3b subclasses were significantly associated with genotypes of the LPL-HindIII polymorphism (22.1, 19.3 and 11.4%, respectively, of sample variance; p < 0.05). Finally, associations were examined between genotypes at the apoAI-CIII-AIV gene cluster and the extent of coronary atherosclerosis. Global severity of atherosclerosis at the first angiography was weakly associated with genotypes of the apoCIII-C/T1100 polymorphism, presence of the T1100 allele being associated with 53% lower median score (1.6 vs 0.75; p = 0.09).(ABSTRACT TRUNCATED AT 400 WORDS)

Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden.

Association studies were carried out on a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms (PvuII, HindIII and Serine447-Stop) at the lipoprotein lipase (LPL) gene locus on among-individual differences in plasma lipid traits and progression of atherosclerosis. Significant linkage disequilibrium was detected between any two of these polymorphisms, with the Stop447 allele being only found on the same chromosome as the rare alleles (no cutting sites) of the PvuII and HindIII polymorphisms. In the healthy individuals, weak associations were found between genotypes of the HindIII polymorphism and triglycerides and the PvuII polymorphism and high density lipoprotein cholesterol explaining 7.4% and 5.6% of sample variance (P = 0.03 and 0.09), respectively. No associations were found between these traits and genotypes of the Serine447-Stop substitution, and thus it is unlikely to be the cause of the associations seen with the PvuII and HindIII polymorphisms even though it truncates the enzyme amino acid sequence. The presence of the rare allele, H-, of the HindIII polymorphism was associated with a smaller variance in triglycerides and both cholesterol and triglycerides in the very low density lipoprotein fraction, and with larger interdependent variation between these lipid traits, and also between LPL activity and these lipid traits. This implies that the H- allele, rather than the Stop447 allele, has the major impact on interdependence between traits which are directly or indirectly influenced by LPL activity. In the healthy individuals who were carriers of the apolipoprotein E2 allele, the inter-dependence between LPL activity and lipid traits was significantly smaller, and that between high density lipoprotein cholesterol and both cholesterol and triglycerides in the very low density lipoprotein fraction was much larger compared with non-carriers (P < 0.05). No significant associations were found between lipid traits or lipase activity and genotypes of the Serine447-Stop substitution. However, in the patients, global severity of coronary atherosclerosis at the first angiography was significantly associated with haplotype combinations of the HindIII and the Serine447-Stop polymorphisms, with the H-Stop haplotype being associated with the highest median score (P = 0.02). The data suggest that variation at the LPL gene locus is associated with a pleiotropic effect, that is not directly mediated by changes in lipids, on severity of coronary atherosclerosis.