Case study of copper poisoning in a British dairy herd.

Following the initial diagnosis of chronic copper poisoning (CCP), the copper (Cu) status of a British dairy herd was investigated. Eight fatal cases of CCP were identified over a 17-month period, from December 1999 to May 2001, involving seven Jersey cows and one Holstein-Friesian; seven cows were dry when CCP occurred. Case diagnostic criteria were necrotising hepatopathy associated with abnormally high liver and kidney Cu concentrations. Analysis of the ration for the high-yielding Jersey cow group revealed about 50 mg Cu/kg dry matter intake (DMI). Risk factors predisposing to fatal CCP were Jersey breed, previous high yield, first two weeks of the dry period and moderately high dietary Cu (greater than 40 mg Cu/kg DMI).

Emergence of suspected type D botulism in ruminants in England and Wales (2001 to 2009), associated with exposure to broiler litter.

Scanning surveillance by the Veterinary Laboratories Agency revealed the emergence of suspected botulism in ruminants in 2003, presented as flaccid paralysis. From 2003 to 2009, 168 cattle and 19 sheep incidents were recorded, with mortality between 5 and 80 per cent. All sheep incidents and 95 per cent of cattle incidents had proximity to broiler litter. From July 2006, the gut contents collected from 74 affected cattle and 10 affected sheep were tested for Clostridium botulinum toxins using mice bioassays and for organisms by culture. Type D toxin was identified in 32 per cent of cattle and 18 per cent of sheep samples. C botulinum type D organisms were identified in 40 per cent of cattle and 30 per cent of sheep samples, but broth from one sample reacted with C and D antisera. Type C botulism has previously been reported more commonly than type D in the UK and has been associated with the use of poultry litter as fertiliser, bedding or feed. The almost exclusive association with C botulinum type D toxins or organisms in the gut contents in this survey suggests a change in the source or epidemiology of botulism in the UK. The source of C botulinum type D was uncertain. Broilers may carry C botulinum type D in their gut flora subclinically. The emergence of a new type D strain, or changes in broiler husbandry and nutrition, medication and other enteric infections may have affected colonisation with C botulinum. Further investigation of poultry and farm environments for sources of type D awaits the development of tests for C botulinum toxins that do not require the use of mice.

Skin closure after total hip replacement: a randomised controlled trial of skin adhesive versus surgical staples.

We undertook a randomised controlled trial to compare the outcomes of skin adhesive and staples for skin closure in total hip replacement. The primary outcome was the cosmetic appearance of the scar at three months using a surgeon-rated visual analogue scale. In all, 90 patients were randomised to skin closure using either skin adhesive (n = 45) or staples (n = 45). Data on demographics, surgical details, infection and oozing were collected during the in-patient stay. Further data on complications, patient satisfaction and evaluation of cosmesis were collected at three-month follow-up, and a photograph of the scar was taken. An orthopaedic and a plastic surgeon independently evaluated the cosmetic appearance of the scars from the photographs. No significant difference was found between groups in the cosmetic appearance of scars at three months (p = 0.172), the occurrence of complications (p = 0.3), or patient satisfaction (p = 0.42). Staples were quicker and easier to use than skin adhesive and also less expensive. Skin adhesive and surgical staples are both effective skin closure methods in total hip replacement.

An evaluation of the copper sequestrated during clotting in cattle: is it just caeruloplasmin?

In cattle, sequestration of copper (Cu) occurs during the clotting process so that serum Cu concentrations are markedly lower than plasma Cu. It has been suggested that all of the Cu lost during clotting is caeruloplasmin (CP). This study used paired samples from 125 cattle to assess whether this assumption was correct. The regression equations for plasma CP activity against plasma Cu concentration and serum CP against serum Cu had significantly different intercepts suggesting that at zero CP activity the amount of Cu remaining was dependent on sample type. Furthermore, the difference between serum and plasma Cu was unrelated to Cu status, whereas the difference between serum and plasma CP was related to Cu status. The regression equation for the loss of CP activity against change in Cu concentration had an intercept that was different from zero, indicating that a reduction in Cu concentration could occur even if CP activity was unaffected by clotting.

The assessment of blood copper status in cattle: a comparison of measurements of caeruloplasmin and elemental copper in serum and plasma.

AIM: To evaluate the effect of test, either copper (Cu) concentration or caeruloplasmin (CP) activity, and sample type, either serum or plasma, on the diagnosis of blood Cu status in cattle. METHODS: Paired serum and heparinised plasma samples taken from 125 cattle in 13 herds were tested for Cu concentration and CP activity. The individual results for serum Cu concentration and serum and plasma CP activities were compared with the plasma Cu concentration results, as were their diagnostic values as determined by reference ranges, i.e. 'marginal', 'adequate', 'excess'. RESULTS: The overall mean serum Cu concentration was 2.92 micromol/L lower than the mean plasma Cu concentration; however, there was significant variability between individual samples, and the 95% limits of agreement ranged from 0.44 micromol/L more to 6.28 micromol/L less. The relationship between CP activity and plasma Cu concentration was less variable; the 95% prediction interval for plasma Cu concentration from CP activity was +/- 2.8 micromol/L, and was unaffected by whether CP activity was measured in plasma or serum. Using the threshold currently recommended for 'marginal' status of <8.0 micromol/L for serum Cu concentration identified a significantly different population of cattle than a threshold of <9.0 micromol/L for plasma samples. Altering the threshold to <7.0 micromol/L for serum Cu concentration produced better agreement. For CP activity, a threshold of 15 IU/L for both serum and plasma identified the same population as a threshold of <9 micromol/L for plasma Cu concentration. CONCLUSIONS: Serum Cu concentration is not a suitable substitute for plasma Cu concentration for the detection of 'marginal' blood Cu status in cattle as the individual variability in the apparent loss of Cu during clotting is too great. In this study, CP activity, in both serum and plasma, was found to be a suitable substitute for the detection of 'marginal' blood Cu status. CLINICAL RELEVANCE: The use of serum Cu concentration rather than plasma Cu concentration in the diagnosis of Cu responsive disease in cattle needs to be re-evaluated as does the way in which individual sample results are used in such tests.

Effects of housing and intake of methionine on the growth and wear of hoof horn and the conformation of the hooves of first-lactation Holstein heifers.

This study investigated the effects of housing primiparous lactating Holstein heifers either in cubicles with butyl rubber mats, cubicles with thicker mattresses filled with chopped rubber, or straw yards, and supplementing them with methionine for the first 13 weeks of lactation on the rates of growth of their hoof horn and the conformation of their feet. Overall, the rate of growth of the hoof horn increased significantly after calving but the rate of wear did not increase. In contrast, the type of housing had no significant effect on the growth of the hoof horn, but the heifers in straw yards had significantly lower rates of lateral horn wear. The changes in growth and wear rates resulted in changes in hoof conformation, including the toe angle and the width of the bearing surface, which suggested that heel bulb hypertrophy occurred after the heifers had been moved from soft underfoot conditions on to concrete. Providing 115 per cent of their estimated methionine requirements had no significant effect on the rates of growth and wear of the hoof horn.

An evaluation of the effect of clotting on the relationship between copper and caeruloplasmin in bovine blood.

The ratio of caeruloplasmin activity to copper concentration (CP:Cu) has been suggested as a more accurate determinant of the requirement for additional copper than plasma or liver copper concentrations. Although this test has no peer-reviewed evidence of efficacy, it has been used by a large number of UK veterinarians. However, the available test uses a serum caeruloplasmin (sCP) activity to plasma copper (pCu) concentration ratio which, because of the preferential loss of caeruloplasmin during clotting, is likely to underestimate the true CP:Cu, although it has been suggested that the marginal range accounts for this. This study was undertaken to evaluate the effect of using serum copper (sCu) rather than pCu concentrations in calculating CP:Cu. Using sCu rather than pCu increased CP:Cu by more than was accounted for by the marginal range. Of 48 cattle which were reported as 'low' using sCP:pCu, 22 were 'normal' when sCu was used instead of pCu. All herds with 'marginal' or 'low' mean CP:Cu when the sCP:pCu concentration ratio was used had 'normal' ratios when sCu was used instead of pCu.

Survey of pigs' kidneys with lesions consistent with PMWS and PDNS and ochratoxicosis. Part 2: pathological and histological findings.

One thousand condemned pigs' kidneys were collected in February 2002 from two pig abattoirs in England to assess the lesions due to postweaning multisystemic wasting syndrome (pmws) and porcine dermatitis and nephropathy syndrome (pdns) and the possible contribution of ochratoxicosis; 174 of the kidneys were pale, 295 were swollen and 81 were abnormally firm with the gross appearance of fibrosis. The main macroscopic finding was the presence of multifocal pale cortical lesions, observed in 446 of the kidneys, and there were large cysts in 266 of them. Histopathological lesions of non-suppurative tubulointerstitial nephritis, with degeneration and fibrosis of renal tubules, were identified in 213 of 250 (85.2 per cent) of the kidneys examined. These lesions were consistent with those reported in cases of pmws and pdns. The tubular degeneration and fibrosis were also consistent with ochratoxicosis. A higher mean concentration of ochratoxin A was significantly (P=0.020) associated with the presence of multifocal pale cortical lesions consistent with ochratoxicosis, but a causal relationship was not confirmed because histochemistry was not used to detect ochratoxin in the lesions directly. There was no significant correlation between the microscopic lesions and the concentration of ochratoxin. The degenerative lesions may have been caused by previous exposure to ochratoxin that had subsequently been excreted, but the microscopic lesions also included non-suppurative interstitial nephritis, which was unlikely to have been caused by ochratoxicosis.

Survey of pigs' kidneys with lesions consistent with PMWS and PDNS and ochratoxicosis. Part 1: concentrations and prevalence of ochratoxin A.

One thousand condemned pigs' kidneys were collected in February 2002 from two pig abattoirs in England to assess the possible contribution of ochratoxicosis to postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS); 250 of the kidneys with macroscopic lesions consistent with nephrosis/nephritis (pale or white cortical lesions) were selected, and the concentration of ochratoxin A was measured in samples of renal cortex by high-performance liquid chromatography (HPLC). Low concentrations were detected in 230 (92 per cent) of the kidneys tested, and in 41 (16.4 per cent) of them the concentration was below the limit of quantification of 0.2 microg/kg. In 187 (74.8 per cent) of the kidneys, the concentration was more than 0.2 microg/kg, and the highest concentration detected was 2.3 microg/kg. The mean (sd) concentration was 0.31 (0.33) microg/kg. The identification of ochratoxin A was confirmed by mass spectrometry. The concentrations of ochratoxin A did not exceed the threshold assessed by the Food Standards Agency to be safe for human food.

Diazinon toxicity in sheep and cattle arising from the misuse of unlicensed and out-of-date products.

Two incidents involving the misuse of unlabelled or out-of-date diazinon products are described. In the first incident, 81 of a group of 210 five-month-old lambs died within 12 hours of being dipped with the contents of a partly used tin of 15-year-old sheep dip. Analysis showed that the diazinon had decomposed by hydrolysis into a range of breakdown products, including tetraethyldithiopyrophosphate (sulfotepp) and monothiono-tetraethylpyrophosphate (monothiono-TEPP), which are much more toxic to mammals than diazinon. In the second incident, four yearling bulls were affected within 48 hours of being treated with a liquid that the farmer believed to be a lice treatment but was actually old diazinon sheep dip. Three of the bulls recovered but one died four days after the treatment. Analysis of the dip confirmed the presence of diazinon but in this incident no breakdown products were detected.

Lead poisoning in cattle and its implications for food safety.

The lead poisoning incidents in cattle investigated by the Veterinary Laboratories Agency between 1990 and 2003 are reviewed. Lead poisoning was most commonly encountered in young calves, but cattle of all ages were affected. The lead was derived mainly from lead paint, lead accumulator batteries and lead in soil from old mine workings. Paint was responsible for the majority of cases of poisoning in young calves; yearling animals were most at risk from discarded batteries, and adult cows were most commonly poisoned by geochemical sources of lead. There was a marked seasonal incidence, with most cases occurring after turnout in the spring and early summer.

An evaluation of the effect of clotting and processing of blood samples on the recovery of copper from bovine blood.

The reference ranges for blood copper (Cu) concentration used by SAC and the UK Veterinary Laboratories Agency have been developed for use with plasma only. Copper sequestration into the clot, primarily in the form of caeruloplasmin, means that serum Cu concentrations are significantly lower than plasma Cu concentrations in the same animals. Serum Cu is commonly used as a surrogate for plasma Cu by applying a proportional conversion factor. However the results of these two studies, which involved a total of 104 pairs of serum and Cu samples from 84 Holstein cattle in one herd, suggest that serum Cu concentrations should not be used in this way. First, the reduction in Cu concentration during clotting was unrelated to initial plasma concentration (varying from 8-59%), which suggests that using a proportional conversion factor is incorrect. Secondly, the correlation between plasma and serum Cu concentration, while significant, was relatively low (r2 proportional 0.6), with the individual variation in Cu loss during clotting ranging from 1.5 to 10.8 micromol/L (mean 4.9 micromol/L). Although this study was undertaken using samples from normocupraemic lactating Holstein cattle in one herd, the data strongly suggest that plasma rather than serum Cu should be used to estimate Cu status unless the laboratory used has developed a reliable serum reference range. We also found that factors other than plasma Cu concentration had a significant effect on loss of Cu during the clotting process. However, no significant effect on the loss of Cu during clotting or by varying the incubation/storage time and temperature of bloods prior to clot removal was noted, nor was there any significant effect of age or Cu intake. Furthermore, when the loss of Cu during clotting was examined in the same heifers at two different timepoints, no correlation between the results was found. Further research is required to establish the factors that affect the loss of Cu during clotting.

Surveillance of suspect animal toxicoses with potential food safety implications in England and Wales between 1990 and 2002.

The potential chemical contamination incidents investigated by the Veterinary Laboratories Agency (VLA) between 1990 and 2002 are reviewed. Incidents were identified in the course of the VLA's surveillance of food animal disease and further investigations were carried out on behalf of the Food Standards Agency in order to identify and control the contamination of food animals and animal products with chemical hazards. In total 876 incidents were investigated, of which 588 involved the poisoning of cattle with heavy metals. There were 63 incidents involving the exposure of cattle, sheep, pigs and poultry to the accidental misuse of veterinary medicines, pesticides or rodenticides, and 50 incidents involving their exposure to microbiological toxins, particularly botulism.

The effect of housing and methionine intake on hoof horn hemorrhages in primiparous lactating Holstein cows.

This study investigated the effects of housing and nutrition on the development of hoof horn disease (as identified by the appearance of hoof horn hemorrhages) in primiparous lactating Holstein cows. The first objective was to investigate whether replacing butyl rubber mats in cubicles (free stalls) with thicker mattresses filled with chopped rubber would significantly reduce hoof horn hemorrhages, and if this reduction would so affect the level of hoof horn hemorrhages as to make it similar to that observed in primiparous cows in straw yards. The second objective was to investigate the effect of methionine supplementation for the first 13 wk of lactation on the development of such hemorrhages. This study confirmed that both sole and white line hemorrhages increase during early lactation in housed cows, although the pattern of development of white line hemorrhages is not identical to that of sole hemorrhages. Housing primiparous cows in straw yards after calving significantly reduced the development of hoof horn hemorrhages, but replacing cubicle mats with thicker mattresses had no significant effect. Providing 115% of calculated methionine requirements had no significant impact on the development of hoof horn hemorrhages.

Relationship between acute phase proteins and hoof horn haemorrhages in postpartum first-lactation heifers.

As part of a study of the development of hoof horn haemorrhages in first-lactation heifers, measurements were made of acute phase reactants to investigate the link between the acute phase response and the development of the haemorrhages. Over a period of two years, blood samples were taken from two separate groups of heifers, weekly in the three weeks before they calved and then twice weekly until eight weeks after calving. Plasma total protein, albumin, fibrinogen, haptoglobin, seromucoid and serum iron and caeruloplasmin were measured and the relationships between the peak concentration (or activity) or the area under the curve of each acute phase reactant and the peak scores for sole or white line haemorrhages were assessed by linear regression. The results suggested that the development of the hoof horn haemorrhages observed in the study was not accompanied by an acute phase response, and the haemorrhages were therefore not primarily caused by endotoxicosis. The diets and husbandry systems used were typical of dairy farms in the UK and the results therefore suggest that a significant proportion of hoof horn haemorrhages observed in UK dairy cows may not be caused by endotoxicosis.