Population dynamics of inherited copper toxicosis in Dutch Bedlington terriers (1977-1997).

Inherited copper toxicosis in Bedlington terriers was 1st reported in 1975 and the entire Dutch population was examined from 1976 until the present for presence of the disease. To examine the effect on the prevalence of the disease of excluding affected dogs from breeding we have compared 2 time cohorts, the 1st consisting of dogs born from January 1, 1976, to January 1, 1986 (n = 155), and the 2nd of dogs born from January 1, 1990, to January 1, 1997 (n = 195). The diagnosis was made in the 1st cohort by evaluating liver biopsies, and in the 2nd cohort with a DNA marker. The population was also resolved into clusters of related dogs to analyze the familial distribution of the disease in the population and to search for ancient founders of the disease among the ancestors of sick dogs. Forty-six percent of dogs examined between 1976 and 1986 had copper toxicosis. Eleven percent of dogs examined in the 2nd cohort had evidence of disease. This reduction was achieved while maintaining the already limited genetic heterogeneity of the population: the number of clusters and the mean relatedness between the clusters were similar in both time cohorts. The disease was evenly distributed over the clusters of related dogs in both cohorts. All ancestors had contributed to the distribution of copper toxicosis and no specific founders could be identified. This indicates that when the breed was established in The Netherlands, the disease was already highly prevalent in the founding dogs.

Familial clustering and risk analysis for fragmented coronoid process and elbow joint incongruity in Bernese Mountain Dogs in The Netherlands.

OBJECTIVE: To analyze familial clustering and genetic risk for various forms of elbow dysplasia (ED) in Bernese Mountain Dogs (BMD) in The Netherlands and define possible means to select against ED. ANIMALS: 98 BMD born in 1992 and 64 BMD born in 1995. PROCEDURE: Dogs were examined radiographically when 12 to 18 months old. The population was resolved into familial clusters, and distribution of ED for the clusters was analyzed. Common ancestors associated with each form of ED were identified, and risk for having ED in the 64 offspring born in 1995 was calculated by relatedness to common ancestors. Risk was compared with radiographic outcome. RESULTS: The 2 forms of ED identified were fragmented coronoid process (FCP) and elbow joint incongruity (INC). Incidence of ED decreased from 63/98 (64%) in 1992 to 29/64 (45%) in 1995. None of the familial clusters was free of FCP or INC. Common ancestors associated with FCP differed from those associated with INC. There was more potential variation in risk for FCP and INC in the 64 offspring than was achieved by breeders, indicating a decrease in population heterogeneity. CONCLUSIONS AND CLINICAL RELEVANCE: FCP and INC had differing familial sources; thus, they most likely are different genetic traits. Although incidence of ED decreased from 1992 through 1995, we did not detect variation among pedigrees in genetic risk for ED remaining in the offspring born in 1995; thus, selection among families cannot further improve ED health status of BMD in The Netherlands. Phenotypic selection within families remains the only alternative.

Prediction of inherited portosystemic shunts in Irish Wolfhounds on the basis of pedigree analysis.

OBJECTIVE: To test validity of prediction for inherited portosystemic shunts (PSS) in Irish Wolfhounds, using nonselective clinical findings and a computerized database containing 5-generation pedigrees. ANIMALS: 613 dogs in the first and 396 dogs in the second cohort. PROCEDURE: Preprandial venous ammonia concentration was measured at 6 to 8 weeks in all pups born between Jan 1, 1988 and Jan 1, 1997 Portosystemic shunts were confirmed in hyperammonemic pups, using radioisotope shunt index measurement, and diagnosis of shunting was confirmed at abdominal surgery or necropsy. Findings in dogs of the first cohort (born before Jan 1, 1992) were used to predict shunting in their offspring of the second cohort. Common ancestors of first-cohort dogs with shunts were tested for positive associations with the disease. Risk for a shunt in all second-cohort dogs was predicted on the basis of relatedness with founders and was compared with outcome of clinical screening. RESULTS: Prevalence of shunts in first and second cohorts was 3.1 and 2.3%, respectively. Fifteen highly related associated founders could be identified. Second-cohort dogs were classified into 6 groups of increasing predicted risk. Mean number of dogs per class was 60; number of clinically diagnosed cases ranged from 0 in the class with the lowest risk to 4 in the highest risk class. CONCLUSIONS: Genetic risk for reproducing a PSS in Irish Wolfhounds was accurate, using the described method. CLINICAL RELEVANCE: Risk estimation provides a tool for genetic counseling, does not require knowledge of the mode of inheritance, and may be valid for any inherited disease.

Effect of GnRH and hCG administration on plasma LH and testosterone concentrations in normal stallions, aged stallions and stallions with lack of libido.

Gonadotrophin-releasing hormone (GnRH) (a single intravenous injection with 0.042 mg busereline acetate) was administered to control stallions (n=5), aged stallions (n=5) and stallions with lack of libido (n=5). Jugular blood samples were taken at -10, 0, 10, 20, 40 and 80 minutes after treatment and measured for luteinizing hormone (LH) and testosterone concentrations. A single intravenous injection of hCG (3000 IE) was given 1 day later. Venous blood samples were taken at -60, 0, 15, 30, 60, 120, and 240 minutes after treatment and measured for the testosterone concentration. The experiment was performed in the breeding season. There was a wide variation between stallions in basal concentrations of LH and testosterone. The treatment groups all showed a significant increase in LH and testosterone concentrations after treatment with GnRH. There was a significant difference (P<0.05) between the control, the lack of libido stallions and the aged stallions in the production of LH before and after stimulation with GnRH. The aged stallions had higher basal LH concentrations. GnRH induced a rise in plasma LH in all groups, but the greatest response was observed in aged stallions. No response to GnRH was seen with respect to plasma testosterone. There was an increase in plasma testosterone following hCG; however, this increase was very small in aged stallions. After stimulation with hCG the control and lack of libido stallions had a significant increase (P<0.05) in testosterone production. In conclusion, stimulation with either GnRH or hCG can be a valuable method to test whether the function of the stallion's reproductive endocrine system is optimal.

Effects of different iron contents in the milk replacer on the development of iron deficiency anaemia in veal calves.

The effect of different iron concentrations in the milk replacer on the development of iron deficiency anaemia during a fattening period of 28 weeks was studied in three groups of 14 calves. The iron contents in the milk replacer differed during the first seven weeks: 60, 100 and 150 mg Fe/kg in groups A, B and C, respectively. In all three groups blood haemoglobin, mean corpuscular volume, plasma iron concentration and saturation decreased during the fattening period, whereas the total iron-binding capacity increased. At week 7, liver iron concentrations were high with a large individual variation [A: 201 (61-706), B: 99 (47-129), C: 296 (77-1572) micrograms/g dry matter]. During the fattening period, liver iron concentrations decreased, with the lowest values at week 25 [A: 54 (34-82), B: 55 (44-83), C: 57 (42-79) micrograms/g dry matter]. Muscle iron concentrations decreased between week 7 and 19. Except plasma iron and saturation in group C, no differences in haematological and tissue iron variables were found throughout the fattening period in spite of different iron contents in the milk replacer during the first seven weeks.

Risk estimates for dichotomous genetic disease traits based on a cohort study of relatedness in purebred dog populations.

As a result of strong selection in closed gene pools, dog breeds represent populations of highly related animals. Prominent founder-effects are responsible for inherited diseases occurring in particular breeds, and each breed may have several breed-related diseases, often with a high incidence. Such inherited diseases are a major problem in purebred dog populations, and probably threaten their survival. On the basis of pedigree information held by the National Kennel Clubs and reliable medical data of a representative longitudinal cohort, estimates have been made of the relative risks of dichotomous disease traits in all combined breeding stock. This approach is independent of assumptions about modes of inheritance or thresholds. In a cohort study, all the common ancestors of the cases are selected and their degree of relatedness to both cases and controls is estimated. The ancestors which are positively associated with the dichotomous disease trait are selected on the basis of scores of relatedness. To reduce the number of parameters, while maintaining maximal informativeness, a principal component analysis is applied. Finally a logistic model, based on the principal components and the case control definitions, describes the most likely pattern of the passage of genetic risk factors down the generations. Estimates of relatedness to seven highly related ancestors were sufficient to describe the distribution of disease in a population of Dutch labrador retrievers. This approach may be used for genetic counselling for any clinical phenotypically dichotomous trait in such a highly related population of companion animals, and may also help to identify suitable dogs for molecular studies of the underlying defect.

Cluster analysis of the genetic heterogeneity and disease distributions in purebred dog populations.

Purebred dog populations have been subject to strong selection which has resulted in extreme differences between breeds and decreased heterogeneity within breeds. As a result, breed-specific inherited diseases have accumulated in many populations. The aim of this study was to analyse genetic heterogeneity in relation to the distribution of elbow dysplasia in labrador retrievers, portosystemic shunts in Irish wolfhounds, and hepatic copper toxicosis, in Bedlington terriers. Decreased heterogeneity was demonstrated in the multiple genetic interrelations in the three populations. In pedigrees containing seven generations of ancestors, the average number of common ancestors in all pair-wise combinations of dogs was five to six (range 0 to 18). These complex interrelationships were resolved by a cluster analysis on matrices of relatedness. This analysis gave clusters of highly related animals, the average relatedness of these clusters, and the average relatedness of the entire population, as expressions of its genetic variability. The mean relatedness was 0.032 for Irish wolfhounds and Bedlington terriers, and 0.002 for labrador retrievers. The labrador retriever cohort was resolved into 31 clusters, and all cases of elbow dysplasia were concentrated in five highly related clusters with an overall incidence of 17 per cent. The Bedlington terrier cohort consisted of 12 clusters which all contained cases of copper toxicosis, with an overall incidence of 46 per cent. The Irish wolfhounds were divided into 14 clusters with a disease incidence of 4 per cent. Dogs with portosystemic shunts were found in four averagely related clusters. A genetic distribution became obvious only when relatedness due to common ancestors of the cases was used as a criterion, and the cases were then concentrated in five highly related clusters.

Prediction of the genetic risk for fragmented coronoid process in labrador retrievers.

In a cohort of 252 Dutch labrador retrievers born between 1988 and 1992, seven founders for fragmented coronoid process were identified. The 185 labrador retrievers born to this cohort between January 1, 1993 and January 1, 1997, were examined clinically, and radiographs of both elbows taken in four directions at 12 to 18 months of age, or earlier when they had signs of lameness, were evaluated. The diagnosis of fragmented coronoid process was confirmed by arthrotomy. The incidence of the condition in the 185 dogs was 17.3 per cent, and for each dog a genetic risk factor was calculated on the basis of its relatedness to the seven founders. The risk factors ranged from 0.07 to 0.41. The dogs were divided into classes of increasing predicted risk, and the mean risk for each class was then compared with the clinical outcome. There were no significant differences between the predicted risk and the outcome in any of the classes.

Yield of embryos in PMSG-superovulated cows treated with anti-PMSG six or 18 hours after the peak of luteinising hormone.

One hundred and forty-six Dutch cross Friesian cows were selected from a local slaughterhouse and synchronised with norgestomet. The 134 cows with a normal progesterone pattern after the removal of the norgestomet implant were treated intramuscularly with 3000 iu pregnant mare's serum gonadotrophin (PMSG) on day 10 followed by 22.5 mg prostaglandin 48 hours later. Blood samples were collected daily and at hourly intervals from 30 to 54 hours after the prostaglandin. The 113 cows with a pre-ovulatory peak of luteinising hormone (LH) were divided into three groups: 37 control cows (group 1) received a placebo six hours after the LH peak; 42 cows (group 2) received anti-PMSG six hours after the LH peak and 34 cows (group 3) received anti-PMSG 18 hours after the LH peak. All the cows were inseminated 10 hours after the LH peak. Six or seven days after insemination the cows were slaughtered and the embryos were evaluated after flushing the ovaries, and the numbers of corpora lutea, cysts and follicles on the donor ovaries were counted. Treatment with anti-PMSG had no significant effect on the numbers of corpora lutea or the numbers of embryos compared with the control group. The mean (+/- sem) numbers of corpora lutea were 14.7 +/- 1.4, 16.3 +/- 1.4 and 16.6 +/- 1.4 for groups 1, 2 and 3, respectively. The numbers of transferable embryos were 3.5 +/- 0.6, 4.1 +/- 0.7 and 5.0 +/- 0.7 for groups 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Relations between on-line electrical conductivity and daily milk production on a low somatic cell count farm.

To study the relation between on-line electrical conductivity and daily milk production, data of 1389 cow days were analyzed. After correction for cow effects and DIM, a rise of 1 mS of the mean electrical conductivity caused a decline of .88 kg/d in milk production. A rise of 1 ln(SCC) unit was associated with an additional decline of .54 kg/d in milk production. In cows without clinical mastitis during the test period, the losses associated with mean electrical conductivity and ln(SCC) were 1.06 and .45 kg/d of milk production, respectively. Electrical conductivity and SCC were associated with daily production loss; the effects were additive. Therefore, electrical conductivity and SCC can be utilized as indirect tests of subclinical mastitis.

Blood hemoglobin, plasma iron, and tissue iron in dams in late gestation, at calving, and in veal calves at delivery and later.

The effect of 100 ppm of Fe in milk replacer on some hematological and tissue Fe variables was studied during the first 7 wk of the fattening period in two groups of eight calves with low or high initial blood hemoglobin concentrations. Hemoglobin concentration in calves with initially low hemoglobin increased. It decreased in those with initially high hemoglobin, but the difference remained over the experimental period. Higher mean liver Fe concentration, in some cases extremely high, and lower mean total Fe-binding capacity were found throughout the experiment in the group with the initial high hemoglobin. Of all variables, only low muscle Fe concentrations were correlated linearly with plasma Fe. In another experiment, the relationship of some hematological and tissue Fe variables during late gestation (about 10 d prepartum), at calving in dams, and at delivery in calves was investigated. The calves showed markedly higher liver Fe concentrations at delivery than their dams just before delivery, but these liver Fe concentrations were not correlated between dam and calf. The hematological and tissue Fe variables showed a weak correlation between dams and calves during late gestation or at delivery. However, dams as well as calves were Fe-sufficient.

Mycobacterium leprae--millennium resistant! Leprosy control on the threshold of a new era.

Over the past decades, the conditions of leprosy control implementation have changed dramatically. Introduction of multidrug therapy, together with the global effort of the World Health Organization to eliminate leprosy as a public health problem, had a tremendous impact on leprosy control, particularly by decreasing the registered prevalence of the disease. At the beginning of the new millennium, leprosy control programmes face several new challenges. These relate not only to changes in the prevalence of the disease, but also to changes in the context of leprosy control, such as those created by health sector reforms and other disease control programmes. This review discusses current knowledge on the epidemiology of Mycobacterium leprae and some important aspects of leprosy control. It is argued that our understanding is still insufficient and that, so far, no consistent evidence exists that the transmission of leprosy has been substantially reduced. Sustainable leprosy control, rather than elimination, should be our goal for the foreseeable future, which also includes care for patients on treatment and for those released from treatment. This, however, requires new strategies.