The effect of genetic defects on pregnancy loss in Swedish dairy cattle.

The effect of carrier status of 10 lethal recessive genetic defects on pregnancy maintenance in Swedish dairy cattle was examined. The genetic defects were Ayrshire Haplotype 1, Ayrshire Haplotype 2, BTA12, BTA23, and Brown Swiss Haplotype 2 in Red Dairy Cattle (RDC), and Holstein Haplotype 1, 3, 4, 6, and 7 (HH1-HH7) in Holstein. Effects of carrier status of BTA12 and HH3 on conception rate (CR), interval from first to last service (FLS), and milk production were also examined. Data were obtained for 1,429 herds in the Swedish milk recording system, while information on carrier status of genetic defects was obtained from the Nordic Cattle Genetic Evaluation. In total, data on 158,795 inseminations in 28,432 RDC and 22,018 Holstein females were available. Data permitted separate analyses of BTA12 and HH3, but carrier frequencies of other defects were too low to enable further analysis. Pregnancy loss was defined as failure to maintain pregnancy, where pregnancy status was confirmed with manual and chemical pregnancy diagnosis, insemination, calving, sales and culling data. Odds ratios (OR) and probabilities of pregnancy loss and CR were estimated using generalized linear mixed models, while pregnancy loss, CR, FLS, milk, protein, and fat yields were analyzed using linear mixed models. Pregnancy losses were reported on average within the first month post-AI. At-risk matings were more prone to suffer pregnancy loss in BTA12 (OR = 1.79) and HH3 carriers (OR = 1.77) than not-at-risk matings. At-risk matings also had lower CR (OR = 0.62 and 0.63 for BTA12 and HH3, respectively) than not-at-risk matings. Carrier females of BTA12 had longer FLS and higher milk production than noncarriers. Conception rate and pregnancy maintenance could be improved by avoiding at-risk matings. This finding could help reduce pregnancy loss due to genetic defects in the breeding program for improved fertility.

Genetic parameters of pregnancy loss in dairy cows estimated from pregnancy-associated glycoproteins in milk.

This study examined the feasibility of using pregnancy-associated glycoproteins (PAG) in milk within breeding for pregnancy maintenance and assessed the genetic variation in pregnancy loss traits. A total of 374,206 PAG samples from 41,889 Swedish Red (SR) and 82,187 Swedish Holstein (SH) cows were collected at monthly test-day milkings in 1,119 Swedish herds. Pregnancy status was defined based on PAG levels and confirmed by data on artificial insemination (AI), calving, and culling from d 1 postinsemination to calving. Pregnancy loss traits were defined as embryonic loss (diagnosed 28 d to 41 d after AI), fetal loss (42 d after AI until calving), and total pregnancy loss. Least squares means (± standard error, %) and genetic parameters were estimated using mixed linear models. Heritability was estimated to be 0.02, 0.02, and 0.03 for embryonic loss, fetal loss, and total pregnancy loss, respectively. Cows with pregnancy loss had lower PAG concentrations than cows which successfully maintained pregnancy and calved. PAG recording was limited to monthly test-day milking, resulting in low estimated embryonic loss (17.5 ± 0.4 and 18.7 ± 0.4 in SR and SH, respectively) and higher fetal loss (32.8 ± 0.5 and 35.1 ± 0.5 in SR and SH, respectively). Pregnancy loss might have occurred earlier but remained undetected until the next test-day milking, when it was recorded as fetal loss rather than embryonic loss. Estimated genetic correlation between embryonic and fetal pregnancy loss traits and classical fertility traits were in general high. Identification of novel genetic traits from PAG data can be highly specific, as PAG are only secreted by the placenta. Thus, PAG could be useful indicators in selection to genetically improve pregnancy maintenance and reduce reproductive losses in milk production. Further studies are needed to clarify how these results could be applied in breeding programs concurrent with selection for classical fertility traits.

Genetic parameters for reproductive losses estimated from in-line milk progesterone profiles in Swedish dairy cattle.

This study assessed the extent of reproductive losses and associated genetic parameters in dairy cattle, using in-line milk progesterone records for 14 Swedish herds collected by DeLaval's Herd Navigator. A total of 330,071 progesterone samples were linked to 10,219 inseminations (AI) from 5,238 lactations in 1,457 Swedish Red and 1,847 Swedish Holstein cows. Pregnancy loss traits were defined as early embryonic loss (1-24 d after AI), late embryonic loss (25-41 d after AI), fetal loss (42 d after AI until calving), and total pregnancy loss (from d 1 after AI until calving). The following classical fertility traits were also analyzed: interval from calving to first service, interval from calving to last service, interval between first and last service, calving interval, and number of inseminations per service period. Least squares means with standard error (LSM ± SE), heritabilities, and genetic correlations were estimated in a mixed linear model. Fixed effects included breed, parity (1, 2, ≥3), estrus cycle number when the AI took place, and a linear regression on 305-d milk yield. Herd by year and season of AI, cow, and permanent environmental effect were considered random effects. Extensive (approximately 45%) early embryonic loss was found, but with no difference between the breeds. Swedish Red was superior to Swedish Holstein in the remaining pregnancy loss traits with, respectively: late embryonic loss of 6.1 ± 1.2% compared with 13.3 ± 1.1%, fetal loss of 7.0 ± 1.2% compared with 12.3 ± 1.2%, and total pregnancy loss of 54.4 ± 1.4% compared with 60.6 ± 1.4%. Swedish Red also had shorter calving to first service and calving to last service than Swedish Holstein. Estimated heritability was 0.03, 0.06, and 0.02 for early embryonic, late embryonic, and total pregnancy loss, respectively. Milk yield was moderately genetically correlated with both early and late embryonic loss (0.52 and 0.39, respectively). The pregnancy loss traits were also correlated with several classical fertility traits (-0.46 to 0.92). In conclusion, Swedish Red cows had lower reproductive loss during late embryonic stage, fetal stage, and in total, and better fertility than Swedish Holstein cows. The heritability estimates for pregnancy loss traits were of the same order of magnitude as previously reported for classical fertility traits. These findings could be valuable in work to determine genetic variation in reproductive loss and its potential usefulness as an alternative fertility trait to be considered in genetic or genomic evaluations.

Genetic parameters of endocrine fertility traits based on in-line milk progesterone profiles in Swedish Red and Holstein dairy cows.

Evaluating fertility traits based on endocrine progesterone profiles is becoming a promising option to improve dairy cow fertility. Several studies have been conducted on endocrine fertility traits, mainly in the Holstein breed. In this study, focusing also on the Swedish Red (SR) breed, genetic parameters were estimated for classical and endocrine fertility traits, the latter based on in-line milk progesterone records obtained for 14 Swedish herds using DeLaval Herd Navigator (DeLaval International, Tumba, Sweden). A total of 210,403 observations from 3,437 lactations of 1,107 SR and 1,538 Holstein cows were used. Mixed linear animal models were used for estimation of genetic parameters. Least squares means analysis showed that Holstein cows had a 2.5-d-shorter interval from calving to commencement of luteal activity (C-LA) and longer length of first inter-ovulatory interval (IOI) than SR cows. The highest mean interval for C-LA, IOI, and first luteal phase length (LPL) was observed in the fourth parity. The incidence of short (<18 d), normal, (18-24 d), and long (>24 d) IOI was 29.3, 40.7, and 30%, respectively. Genetic analysis indicated moderate heritability (h2) for C-LA (h2 = 0.24), luteal activity during the first 60 d in milk (LA60, h2 = 0.15), proportion of samples with luteal activity (PLA, h2 = 0.13), and calving to first heat (CFH, h2 = 0.18), and low heritability estimates for LPL (h2 = 0.08) and IOI (h2 = 0.03) in the combined data set for both breeds. Similar heritability estimates were obtained for each breed separately except for IOI and LPL in SR cows, for which heritability was estimated to be zero. Swedish Red cows had 0.01 to 0.06 higher heritability estimates for C-LA, LA60, and PLA than did Holstein cows. Calving interval had moderate heritability among the classical traits for Holstein and the combined data set, but h2 was zero for SR. Commencement of luteal activity had a strong genetic correlation with LA60 (mean ± SE; -0.88 ± 0.06), PLA (-0.72 ± 0.11), and CFH (0.90 ± 0.04). Similarly, CFH had a strong genetic correlation with IOI (0.98 ± 0.20). Number of inseminations per series showed a weak genetic correlation with all endocrine traits except IOI. Overall, endocrine traits had higher heritability estimates than classical traits in both breeds, and may have a better potential to explain the actual reproductive status of dairy cows than classical traits. This might favor inclusion of some endocrine fertility traits-especially those related to commencement of luteal activity-as selection criteria and breeding goal traits if recording becomes more common in herds. Further studies on genetic and genomic evaluations for endocrine fertility traits may help to provide firm conclusions. A prerequisite is that the data from automatic devices be made available to recording and breeding organizations in the future and included in a central database.

Urea clearance: a new technique based on microdialysis to assess liver blood flow studied in a pig model of ischemia/reperfusion.

Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

Segmental ischemia of the liver - microdialysis in a novel porcine model.

BACKGROUND: Segmental liver ischemia is often used in rodents to study ischemia and reperfusion injuries (IRI). There are no reports of protocols using segmental ischemia in porcine models. Microdialysis (MD) provides the opportunity to study local effects of IRI in vivo. METHODS: Eight pigs received an MD catheter placed in liver segments IV and V, respectively. All circulation to segment IV was stopped for 80 min, and reperfusion was followed for 240 min. RESULTS: During ischemia the levels of lactate, glycerol and glucose increased 3-fold (p < 0.001), 40-fold (p < 0.001) and 4-fold (p < 0.01), respectively, in the ischemic segment compared to the perfused segment, whereas the levels of pyruvate fell to a tenth of the preischemic level (p < 0.001). All values returned to baseline after reperfusion. Serum levels of aspartate aminotransferase increased (p < 0.05). Polymorphonuclear cells increased in both segments, although the density was significantly higher in segment IV. CONCLUSION: Clamping of one liver segment in pigs is a simple, stable and reproducible model to study IRI with minimal systemic effects. MD revealed no signs of anaerobic metabolism in the perfused segment but still there was an increase in the number of polymorphonuclear neutrophils in this segment, although it was lower than that in the ischemic segment.

Standardized CT examination of the multitraumatized patient.

The aim of this study was to develop a standardized non-helical-CT protocol including head, body and proximal extremities in order to achieve a good time efficiency and diagnostic accuracy in the initial radiological evaluation of the multitraumatized patient. A total of 111 circulatory stable blunt trauma patients, brought in to a trauma level II-III hospital, were examined according to a standardized CT protocol. After examining the head with contiguous 10-mm slices without i.v. contrast medium injection, the trunk was examined with 10-mm slices every 30 mm through thorax-abdomen-pelvis with i.v. contrast medium enhancement (occasionally modified). All data in the medical reports were collected and used as "end-point", and the outcome of the CT examination was compared with this final diagnosis. Mean examination time was 20 min (range 12-32 min). In total, 55 head injuries, 89 thoracic injuries, 27 abdominal/pelvic injuries and 62 fractures were found. Computed tomography correctly identified the injuries, except one brain stem injury, one contusion/rupture of the heart, one hepatic injury, two intestinal injuries, eight vertebral injuries and one joint dislocation. A standardized non-helical-CT examination of the head and body may be achieved in 20 min. Its diagnostic accuracy was high, except for vertebral column injuries, which is why we recommend it as the method of choice for initial radiological examination of multitraumatized patients. When available, helical scanning would improve both examination speed and accuracy.

Serum proteins in liver cirrhosis: effects of shunt surgery.

The serum protein patterns of 38 patients with alcoholic liver cirrhosis were studied and compared with those of 15 patients with cryptogenic cirrhosis and of 18 normal volunteers. Serum prealbumin and albumin were significantly lowered in alcoholic liver cirrhosis in comparison with the normals. In liver cirrhosis, the four acute phase reactants, alpha 1-antiproteinase, orosomucoid, and haptoglobin and caeruloplasmin, showed a pattern in serum, in which alpha 1-antiproteinase was increased, orosomucoid and haptoglobin were decreased, and caeruloplasmin was normal. Immunoglobulins G, A and M were significantly elevated. IgA was significantly more elevated in patients with alcoholic disease than in patients with cryptogenic cirrhosis. The construction of a surgical portal-systemic shunt resulted in a significant decrease in serum concentrations of the acute phase reactants, while prealbumin, albumin and immunoglobulins were unaffected.

Nonoperative treatment of blunt trauma to liver and spleen.

Nonoperative management of 20 cases of liver injury in 1969-1984 and 13 of splenic injury in 1977-1984, all due to blunt abdominal trauma, is retrospectively reviewed. The total of blunt hepatic injuries treated in the same period was 63 and that of blunt splenic injuries 52. There were no major differences in etiology, age, sex distribution or need for blood transfusion between the liver and splenic trauma cases. After initial resuscitation and diagnostic work-up with angiography, computed tomography, ultrasonography and/or scintiscan, circulatorily stable patients were selected for nonoperative treatment. These patients showed evidence of mild trauma with few associated major injuries, few complications and no mortality. Following initial bedrest and observation, they were gradually mobilized and could leave the hospital after about 2 weeks.

Portal-systemic encephalopathy. Influence of shunt surgery and relations to serum amino acids.

Fifty patients with liver cirrhosis, portal hypertension, and a history of bleeding oesophageal varices underwent 15 different cognitive psychometric tests to evaluate the presence of subclinical portal-systemic encephalopathy. None of the patients were clinically encephalopathic. The patients were compared with 50 healthy control subjects. Twenty-three patients showed definite signs of encephalopathy in the psychometric tests, 17 were normal, and 10 were borderline cases. The most pronounced abnormalities were seen in tests reflecting logic inductive capacity, visual spatial performance, cognitive flexibility, perceptual speed, spatial perceptive ability, and psychomotor performance. Tests reflecting word memory were less affected. Serum liver function tests did not differ between patients with deranged and normal brain functions. The serum isoleucine concentration was, however, significantly lower in the encephalopathic patients. The psychometric test results did not differ between patients with alcoholic and nonalcoholic liver cirrhosis, and no change was noted 2 years after shunt surgery.

Prophylactic effect of human immunoglobulin against pneumococcal post-splenectomy sepsis in the rat.

Failure to clear the blood of pneumococci after splenectomy may be corrected by active immunization, but some patients show poor antibody response to pneumococcal vaccination. Long-term antibiotic prophylaxis against post-splenectomy sepsis carries the risk of development of bacterial resistance and low patient compliance. In the present study, using a rat model for post-splenectomy sepsis, human immunoglobulin was given 24 h before challenging the animals with 10(3) Streptococcus pneumoniae. Immunoglobulin at a dosage of 300 mg/kg body weight was protective. Reducing the immunoglobulin dose to 75 mg/kg did not alter the mortality rate but significantly prolonged the survival time. The results indicate that the new immunoglobulin preparations for intravenous use might provide an effective means of reducing the risk of post-splenectomy sepsis, even in the most susceptible patients.

Treatment of pneumococcal postsplenectomy sepsis in the rat with human gamma-globulin.

A rat model was used to evaluate the possible effect on experimental postsplenectomy sepsis of a human gamma-globulin preparation for intravenous use (Sandoglobulin). Sixty splenectomized male Sprague-Dawley rats were given 3 X 10(3) Streptococcus pneumoniae type 1 intravenously. Twelve of the animals received no treatment and all died, in contrast to 12 sham-operated controls which all survived the challenge. The remaining splenectomized rats were divided into four groups, each consisting of 12 animals. One group was given 120 mg human gamma-globulin twice intraperitoneally (0.3 g/kg body wt), at 18 and 42 hr, after challenge; 10 of the 12 survived, in contrast to none of the 12 in the second group receiving 120 mg human albumin instead of gamma-globulin (P = 0.00003). When the injections were delayed to 24 and 48 hr, 9/12 gamma-globulin-treated animals still survived, in contrast to 0/12 in the albumin group. These findings point to new possibilities for treatment and perhaps prevention of overwhelming postsplenectomy sepsis by administration of high doses of gamma-globulins.

Effect of gamma globulin infusion on type-specific pneumococcal antibody levels in splenectomized adults.

Using an ELISA technique, changes in specific antibody levels against pneumococcal serotypes 1, 4, 7F, 14, 18C and 23F were studied in 8 adults healthy at the time of investigation but splenectomized previously because of hematological disease following infusion of 200 mg/kg body weight of a commercially available immunoglobulin preparation for intravenous use (Sandoglobulin). Among the 4 patients with initially low serum levels of antipneumococcal antibodies, significantly raised antibody levels were demonstrated against type 14 for 8 weeks. On the other hand, the infusion did not lead to increased antibody levels in 3 patients with high preinfusion values for antipneumococcal antibodies. In contrast, a significantly lower antibody value for type 7F was recorded 3 weeks after infusion. Efficacy of immunoglobulin prophylaxis is, therefore, probably doubtful in certain splenectomized patients, and if contemplated should be preceded by analysis of antibody levels against common pathogens.

Hypersplenism--effect on haemostasis. An experimental study in the rat.

Hypersplenism induced by methylcellulose given to rats i.p. was characterized by splenomegaly, anaemia, leucocytopenia and thrombocytopenia. Hb, Hct and WBC count were normalized, and platelet count rose to supernormal values by splenectomy. At a standardized liver resection, the hypersplenic rats had an increased blood loss and prolonged bleeding time in comparison with control rats. Removal of the large spleen normalized these abnormalities. Hypersplenism also shortened APT time and impaired ADP and collagen-induced platelet aggregation, findings not normalized by splenectomy.

Comparison of antibody levels and protective efficacy against pneumococci in two immunoglobulin preparations for intravenous use.

Passive immunization with modern intravenous immunoglobulin preparations might be used prophylactically in individuals at extreme risk of contracting postsplenectomy sepsis or therapeutically in established infections. Since pneumococci are the predominant causative organisms, we determined antibodies against 14 pneumococcal serotypes in two commercially available immunoglobulin preparations (two batches of each) using enzyme-linked immunosorbent assay. The four batches were remarkably similar in antibody content. Low levels against some clinically important serotypes, i.e. types 3, 8 and 18C were recorded. The protective effect of one batch of each preparation against type 1 pneumococci was documented in splenectomized rats.

Synergism between gammaglobulin prophylaxis and penicillin treatment in experimental post-splenectomy sepsis in the rat.

In spite of long-term antibiotic prophylaxis and pneumococcal vaccination, there still exists a proportion of highly susceptible splenectomized or functionally hyposplenic patients at risk of contracting fatal overwhelming infections. We have studied the effect of gammaglobulin prophylaxis in experimental sepsis among splenectomized rats. Administration of 37.5 mg human gammaglobulin/kg body weight 24 h before challenge with 10(3) pneumococci resulted in the survival of 19 of 24 rats, in contrast to 1 of 24 controls. A dose of 19 mg/kg body weight was not protective (7 of 23 survived). However, treatment with penicillin 18 h after challenge in the gammaglobulin-pretreated group of animals saved 21 of 24 animals, although penicillin without gammaglobulin prophylaxis showed no effect. These data indicate that even relatively low circulating concentrations of specific antibody after gammaglobulin prophylaxis might nonetheless be adequate to render septic disease easier to treat.