PrP genotype progression in flocks participating in the National Scrapie Plan for Great Britain.

The National Scrapie Plan (NSP) for Great Britain is a voluntary scheme that, through PrP genotype testing and restricted breeding, aims to reduce the risk of scrapie in the national sheep flock. To gauge the progress in member flocks and within breeds, the genotype profile of successive crops of ram lambs was monitored between 2002 and 2004. In each of the 11 most frequently sampled breeds, the proportion of ram lambs testing in the most resistant genotype category (NSP type 1: ARR/ARR) increased, and there was a reduction in the proportion of genotypes associated with the highest disease risk, that is X/VRQ, where X is an allele other than ARR. Changes in the proportion of ram lambs testing for ARR-heterozygous genotypes (NSP type 2: ARR/X, where X is not VRQ) appeared to be influenced by whether the sheep were hill breeds or non-hill breeds. In each of six frequently sampled hill breeds these genotypes expanded, in relative terms, whereas they declined in four of five prominent lowland/crossing breeds. The proportion of ram lambs that carried neither ARR nor VRQ (NSP type 3) declined consistently in the top 11 breeds, but there was little change in the ARR/VRQ genotype (NSP type 4). Among individual flocks that had ram lambs tested in all three years 2002 to 2004, the majority experienced an increase in the proportion testing ARR/ARR, and of those that had VRQ ram lambs in 2002, most recorded a decrease in their frequency by 2004.

Orthotopic heart transplantation in a transgenic pig-to-primate model.

BACKGROUND: Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS: Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS: Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS: The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.

DPI 201-106 for severe congestive heart failure.

DPI 201-106 is a new oral inotropic agent that exerts its effects through a novel mechanism of action, namely, by enhancing sensitivity of myofilaments to calcium and prolonging inward sodium current. In a double-blind, randomized, placebo-controlled fashion, single oral doses (80 and 100 mg) of DPI 201-106 were administered to 15 patients with severe congestive heart failure. Dose-dependent increases in cardiac index (25%, p = 0.016), left ventricular stroke work index (24%, p = 0.018), left ventricular stroke volume index (32%,p = 0.005) and QTc interval (7%, p = 0.009) were observed. Significant effects on heart rate and systemic arterial pressure were not observed. Positive correlations of QTc interval with DPI plasma level (r = 0.64, p = 0.0001), stroke work index (r = 0.47, p = 0.0001) and ventricular ectopic activity on ambulatory electrocardiography (r = 0.49, p = 0.0001) were observed. Maximum changes occurred approximately 3 to 4 hours after ingestion and lasted more than 8 hours. Plasma drug levels were consistent with a 2-compartment model exhibiting first-order absorption and elimination kinetics. DPI 201-106 produced hemodynamic improvement in patients with severe congestive heart failure.

Relationship between serum immunoglobulin values and incidence of respiratory disease in calves.

Severe respiratory disease, with high morbidity and high mortality, occurred in 2 groups of bull calves (14 to 64 days old) raised in th same facility. Necropsy findings included lesions of acute or chronic bronchopneumonia. Serum immunoglobulin G (IgG) values were determined for all calves at 3 to 6 days of age. Calves that died of respiratory disease had an average IgG value of 1,267 mg/100 ml, whereas calves that lived had an average IgG value of 2,698 mg/100 ml. Calves with low serum IgG values had higher morbidity, had to be treated earlier in life, and had to be treated more frequently per day, when compared with calves that had high serum IgG values.

Risk factors associated with extended spectrum beta-lactamase Escherichia coli (CTX-M) on dairy farms in North West England and North Wales.

This study investigated the potential spread of CTX-M-14 Escherichia coli from a known ESBL E. coli positive farm and risk factors for the presence of CTX-M E. coli on dairy farms. Between November 2009 and March 2010, 65 farms in North West England and North Wales were visited and animals sampled for E. coli producing CTX-M ESBLs. Seventeen of these were known to have received animals from a known ESBL E. coli positive 'index' farm since 2005 (linked farms). The prevalence of CTX-M E. coli in the population of linked farms was 58.8% (10/17; CI(95%) 32.9-81.6%) and in the randomly selected control population was 35.4% (17/48; CI(95%) 22.2-50.5%). There was no significant (p>0.05) linkage for the detection of any CTX-M E. coli or specifically a CTX-M-14 E. coli to the index farm. Group 1 (CTX-M-15, CTX-M-55, CTX-M-1, CTX-M-32), group 2 (CTX-M-2) and group 9 (CTX-M-14, CTX-M-14 B, CTX-M-27) CTX-M E. coli were identified on the study farms. Molecular analysis revealed that three plasmids from linked farms had similar sizes (95 kbp), replicon type (IncK) and backbone genes as that from the index farm. Logistic regression analysis revealed that farms that had used a 3rd or 4th generation cephalosporin (ceftiofur, cefoperazone and cefquinome) in livestock in the last 12 months were nearly 4 times more likely to have ESBL E. coli present (p=0.037; OR=3.93). There was no significant association between presence of CTX-M E. coli and the use of any 1st or 2nd generation cephalosporins. Several other risk factors for the presence of CTX-M E. coli were identified, such as storage of slurry in a pit, operating an open herd policy and infrequent cleaning of calf feeding equipment.

Nutritional idiosyncrasies of the golden hamster (Mesocricetus auratus).

The golden hamster has a compartmentalized stomach consisting of a forestomach and a glandular stomach. The forestomach is lined with keratinized epithelium and contains an active microbiol population capable of significant cellulolytic activity. This organ is not essential for life and is the first entrance point for swallowed feed. The hamster, while having a protein requirement like that of the rat, utilizes protein much differently. It ranks soybean meal above a fish protein concentrate and does not utilize added crystalline essential amino acids as such. Acceptance of the hamster as a nutritional surrogate of the rat seems unwarranted.

Influence of neonatal colostrum administration, immunoglobulin, and continued feeding of colostrum on calf gain, health, and serum protein.

Holstein calves (159) were assigned alternately to one of seven regimens through, day 45: nurse dam for 12 to 24 h, dam's milk to 96 h, milk replacer with all milk protein; low (less than or equal to 45 mg/ml) immunoglobulin colostrum to 96 h, then either colostrum, replacer with all milk, or soy protein; high (less than 60 mg/ml) immunoglobulin colostrum to 96 h, then replacer all milk; replacer all milk protein from birth; or saleable milk from birth. Colostrum immunoglobulin was estimated by colostrometer and colostrum was frozen. Starter and water were offered free choice on day 5. Calves deprived of colostrum gained poorly and suffered severe and long scour episodes and high mortality. No differences of body weight gains were observed between calves that nursed compared with those hand fed. Calves fed colostrum with high immunoglobulin gained weight from birth to day 4 while those fed low lost weight. Overall severity and duration of scours were less for calves fed colostrum with high compared to low immunoglobulin. Calves fed undiluted colostrum (5 to 45 days) had more severe scours longer than those fed milk replacer. Serum protein and immunoglobulin were higher for calves hand fed high immunoglobulin compared to low immunoglobulin colostrum or nursing at 12 to 24 h and 4 days after birth. A positive relationship developed between serum protein and immunoglobulin at 12 h to 24 h, 4 and 11 days. Mortality was low for all calves receiving colostrum.

Influence of magnesium, water, and sodium chloride on urolithiasis in veal calves.

Forty veal calves were fed milk replacers containing differing concentrations of Mg in a 16-w study. The concentrations were .1% (basal), .3%, .6% Mg, and .6% Mg plus 2% NaCl. The four groups were further subdivided into two groups fed reconstituted milk replacer at 14 or 17.9% DM. Weight gain was greater at the two lower concentrations of Mg. Calves fed .6% Mg or .6% Mg plus NaCl excreted significantly more Mg than calves fed .1 or .3% magnesium. The low water group (17.9% DM) excreted a more concentrated urine relative to Mg, Ca, and P than did the high water group (14% DM). No urethral obstructions were observed. Seventy percent of calves at .6% Mg and 30% of calves at .6% Mg plus NaCl had stones in their kidneys consisting primarily of calcium apatite and secondarily of struvite. Added NaCl reduced kidney and bladder calculi formation. When high amounts of water were fed, added NaCl prevented calculi formation completely. All calves fed the NRC level of .1% Mg performed normally.

Dietary magnesium and urolithiasis in growing calves.

The effect of high levels of dietary magnesium (1.4%) alone or in combination with elevated calcium (1.8%) or phosphorus (1.6%) on growth and health of male calves was evaluated during a nine week feeding trial after weaning. Twenty calves were randomly divided into 4 feeding groups consisting of controls, high magnesium, high magnesium and calcium or high magnesium and phosphorus. Elevated dietary minerals caused decreased feed intake and growth rate. Blood urea nitrogen and serum creatinine levels were greatly elevated in calves fed high magnesium or magnesium and phosphorus and serum urea nitrogen was moderately elevated in calves fed high magnesium and calcium. These elevations suggested the occurrence of renal damage as a result of microcrystalline obstruction of renal tubules. Serum magnesium levels were three times normal in calves fed high magnesium or magnesium and phosphorus, but only twice normal in calves fed high magnesium and calcium. High dietary magnesium resulted in a significant depression in blood calcium level. This effect was somewhat overcome by additional dietary calcium Three calves fed the high magnesium diet and two calves fed the high magnesium and phosphorus diet developed urinary tract obstruction. The chemical composition of uroliths recovered from these calves was calcium apatite. Elevated dietary magnesium has been shown to be a cause of urolithiasis in growing male calves. Additional dietary calcium, but not phosphorus, appears to protect calves against urolithiasis induced by elevated dietary magnesium.