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Objective: To evaluate the use of a handheld device for measurement of β-hydroxybutyrate (BHBA) concentration to identify prepartum dairy cattle at risk of developing hyperketonemia during the first week after parturition., Design: Cross-sectional study. Animals-210 prepartum dairy cows from 6 herds., Procedures: A blood sample was collected from each cow 3 to 9 days before its expected calving date. β-Hydroxybutyrate concentration was immediately measured with a handheld device. Serum was harvested from the remaining sample and submitted to a laboratory for measurement of BHBA and nonesterified fatty acid (NEFA) concentrations. β-Hydroxybutyrate concentration determined with the handheld device was compared with that determined by laboratory methods. The association between prepartum BHBA concentration and the development of hyperketonemia (BHBA concentration, ≥ 1.2 mmol/L) during the first week after parturition was determined. The agreement between prepartum BHBA and NEFA concentrations for identification of cows at risk of developing postpartum hyperketonemia was evaluated., Results: β-Hydroxybutyrate concentration determined by the handheld device was moderately correlated with that determined by laboratory methods. Cows with a prepartum BHBA concentration ≥ 0.6 mmol/L were 2.2 times as likely to develop hyperketonemia within 1 week after parturition as were cows with a prepartum BHBA concentration < 0.6 mmol/L. There was substantial agreement between prepartum BHBA and NEFA concentrations for identification of cows at risk of developing postpartum hyperketonemia., Conclusions and Clinical Relevance: Results indicated the handheld device was a valid tool for measurement of BHBA concentration in prepartum dairy cattle, and measurement of prepartum BHBA concentration may be helpful for identifying cows at risk of developing postpartum hyperketonemia.

Objective: To determine the association between urine osmolality and specific gravity (USG) in dogs and to evaluate the effect of commonly measured urine solutes on that association., Animals: 60 dogs evaluated by an internal medicine service., Procedures: From each dog, urine was obtained by cystocentesis and USG was determined with a refractometer. The sample was divided, and one aliquot was sent to a diagnostic laboratory for urinalysis and the other was frozen at -80°C until osmolality was determined. Urine samples were thawed and osmolality was measured in duplicate with a freezing-point depression osmometer. The correlation between mean urine osmolality and USG was determined; the effect of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on this relationship was investigated with multiple regression analysis., Results: The Pearson correlation coefficient between urine osmolality and USG was 0.87. The final multivariable regression model for urine osmolality included USG and the presence of ketones; ketonuria had a small negative association with urine osmolality., Conclusions and Clinical Relevance: Results indicated a strong linear correlation between osmolality and USG in urine samples obtained from dogs with various pathological conditions, and ketonuria had a small negative effect on that correlation.

Objective: To determine overall survival time and identify prognostic factors associated with survival time in cats with newly diagnosed diabetes mellitus., Design: Retrospective case series., Animals: 114 cats with newly diagnosed diabetes mellitus., Procedures: Data for analysis included history, signalment, physical examination findings, hematologic and serum biochemical data, presence of ketoacidosis, and diagnosis of concurrent diseases at initial evaluation. The effects of possible predictors on survival time were determined by calculating hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Median survival time of diabetic cats was 516 days (range, 1 to 3,468 days); 70%, 64%, and 46% lived longer than 3, 6, and 24 months, respectively. Survival time was significantly shorter for cats with higher creatinine concentrations, with a hazard of dying approximately 5% greater for each increase of 10 μg/dL in serum creatinine concentration (adjusted HR, 1.005; 95% CI, 1.003 to 1.007). Ketoacidosis was not significantly associated with survival time (HR, 1.02; 95% CI, 0.590 to 1.78)., Conclusions and Clinical Relevance: Cats with newly diagnosed diabetes mellitus had a fair to good prognosis. High serum creatinine concentration at diagnosis was associated with a poor outcome, likely because of the adverse effects of renal dysfunction. Ketoacidosis apparently was not associated with decreased survival time, suggesting that this complication should not necessarily be regarded as unfavorable.

Objective: To evaluate the use of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations in pooled serum samples for herd-based detection of subclinical ketosis (SCK) in dairy cows after calving., Design: Cross-sectional study., Animals: 1,100 dairy cows from 110 herds., Procedures: Blood samples were collected from 10 healthy cows/herd in the first week after parturition. Aliquots of serum were mixed to create a pooled sample. Concentrations of NEFA and BHBA were measured to estimate prevalence of SCK. Pooled sample test results were compared with those obtained for individual samples. Linear regression and receiver-operating characteristic curve analysis were performed; Bland-Altman plots were used to evaluate agreement between methods., Results: Overall prevalence of SCK was 30.7%, 19.3%, and 13.6%, as determined by use of BHBA threshold concentrations of 1,000, 1,200, and 1,400 μmol/L, respectively. Pooled sample concentrations of NEFA and BHBA were significantly correlated (r = 0.98 and 0.97, respectively) with individual sample means and with the number of cows that had NEFA (R(2) range, 0.81 to 0.84) or BHBA (R(2) range, 0.65 to 0.76) concentrations above predefined thresholds. Pooled sample concentrations of NEFA and BHBA were very accurate to highly accurate for herd-based detection of SCK., Conclusions and Clinical Relevance: Analysis of NEFA and BHBA concentrations in pooled serum samples was useful for herd-based detection of SCK. A sample size of 10 cows/herd was deemed adequate for monitoring dairy herds for SCK. Reference criteria specific to pooled samples should be used for this type of herd-based testing.

Objective: To detect changes in serum lipoprotein and apolipoprotein profiles via precipitation and electrophoresis in ketotic cows and in those cows treated with different methods., Animals: 21 cows with clinical and subclinical ketosis, 7 healthy cows in the early lactation period, and 7 healthy cows in the nonlactation period., Procedures: Ketotic cows were allocated into 3 groups; the first group was treated with dextrose and dexamethasone, the second group with dextrose and prednisolone, and the third group with dextrose and insulin. The beta and alpha lipoproteins were precipitated with dextran sulfate-magnesium chloride in ketotic cows after treatment and healthy cows in the nonlactation and lactation periods. The serum samples, precipitates, and supernatants were examined via agarose gel electrophoresis for detection of alterations in serum lipoproteins. Subsequently, alterations in serum apolipoproteins were detected via SDS-PAGE of precipitates., Results: Compared with serum beta and alpha lipoprotein concentrations in healthy cows during nonlactation, those in cows during lactation were higher; however, those in cows with ketosis were lower. The SDS-PAGE analysis of serum beta lipoproteins revealed that apolipoprotein E (approx 36 and 40 kDa) decreased in ketotic cows, in comparison with healthy cows in the nonlactation and lactation periods, but increased after treatment. Decreases in apolipo-protein B (approx 222 kDa), apolipoprotein A-I (19 and 24 kDa), apolipoprotein A-IV (55 kDa), apolipoprotein C-III (8.8 and 10.2 kDa), and albumin (66 kDa) concentrations were detected in ketotic cows, in comparison with the healthy cows in the lactation period., Conclusions and Clinical Relevance: Serum lipoprotein and apolipoproteins may routinely be determined via precipitation and electrophoresis in the diagnosis and treatment of ketosis.

Objective: To use threshold concentrations of acetone and beta-hydroxybutyrate in milk and serum, respectively; identify risk for ketosis and endometritis; and assess analyses of blood and milk samples as predictors of risk for ketosis in high-yielding dairy cows., Animals: 90 multiparous Holstein cows., Procedure: At intervals before and after parturition, blood samples were obtained for determination of glucose, nonesterified fatty acids, leptin, insulin, insulin-like growth factor-1, and beta-hydroxybutyrate concentrations. Samples of milk were obtained at similar intervals after parturition for determination of fat content and concentrations of acetone, protein, and lactose. Reproductive examination of each cow was performed weekly., Results: For each cow, threshold concentrations of acetone and beta-hydroxybutyrate were calculated as 75th and 90th percentiles of maximum postpartum concentrations of acetone in milk (0.40 and 0.87 mmol/L) and beta-hydroxybutyrate in serum (2.30 and 3.51 mmol/L). Significant decrease in milk production (442 to 654 kg of energy-corrected milk/305-day period per cow) was associated with acetone or beta-hydroxybutyrate in excess of threshold values. Milk acetone concentrations > 0.40 mmol/L were associated with 3.2 times higher risk for endometritis. Low plasma glucose, high serum beta-hydroxybutyrate, and high milk acetone concentrations during week 1 after parturition were indicators of increased risk for ketosis later during lactation., Conclusions and Clinical Relevance: Determination of milk acetone concentration during the week after parturition may identify cows at risk for ketosis and endometritis; with appropriate interventions, development of disease and production losses may be reduced.

Objective: To assess effects on functions of peripheral blood mononuclear cells (PBMC) obtained from ewes for each of several fatty acids represented in ovine plasma at concentrations mimicking those of ketotic or healthy ewes., Sample Population: Blood samples obtained from 6 Sardinian ewes., Procedure: The PBMC were cultured in media that contained oleic (OA), palmitic (PA), stearic (SA), linoleic (LA), or palmitoleic (POA) acid at concentrations similar to those of ketotic or healthy ewes. Synthesis of DNA was stimulated by use of concanavalin A or pokeweed mitogen (PWM). Secretion of IgM was stimulated by use of PWM., Results: High concentrations (900, 450, and 225 micromol/L) of OA significantly inhibited DNA synthesis and IgM secretion of PBMC. Conversely, low concentrations (56 or 28 micromol/L) of OA significantly enhanced DNA synthesis of PBMC. High concentrations of PA (600, 300, 150, 75, 375, or 18.7 micromol/L) and SA (300, 150, or 75 micromol/L) significantly inhibited DNA synthesis of PBMC. High concentrations of PA (600, 300, 150, 75, 375, or 18.7 micromol/L) and SA (300, 150, 75, or 38 micromol/L) also significantly inhibited IgM secretion of PBMC. None of the concentrations of LA and POA affected PBMC functions., Conclusion and Clinical Relevance: Impaired immunoresponsiveness of ketotic ewes is likely associated with an increase of plasma concentrations of OA, PA, or SA and not with that of LA or POA. At physiologic concentrations, single fatty acids are likely to participate in modulation of immunoresponsiveness by exerting suppressive or stimulatory effects on immune cells.

Objective: To evaluate the effect of a single dose of recombinant bovine somatotropin (bST) on certain metabolic values, health, and milk production of dairy cows undergoing surgery for left displacement of the abomasum., Design: Blinded clinical trial., Animals: 413 cows with left displacement of the abomasum., Procedure: A single 500-mg dose of bST was administered to dairy cows following surgery in field practice conditions for left displacement of the abomasum. A placebo of the same carrier without bST was administered to control cows in this blinded study. Metabolic and production responses in a short-term follow-up period were measured., Results: Blood glucose concentrations in cows 3 to 5 days after surgery were statistically higher for treated cows than for control cows. A higher proportion of treated cows had improved urine ketone test results than did controls. Significant differences in other metabolic values, health, and milk production were not detected., Clinical Implications: Treatment of metabolically compromised cows with bST may have some positive effects, but further investigation is needed to confirm therapeutic value.

Objective: To assess the relevance of hepatic lipidosis (fatty liver) in the development of ketosis and left displacement of the abomasum (LDA)., Sample Population: Sera from 22 healthy cows in early lactation, 21 cows with ketosis, and 19 cows with LDA, and serum and liver specimens from 35 slaughtered cows with or without fatty liver, ketosis, and/or LDA., Procedure: Apolipoprotein B-100 and A-I concentrations were measured in sera of healthy farm cows and of farm cows with ketosis and LDA. Serum apolipoprotein concentration, together with liver triglyceride content, also were surveyed in a subset of slaughtered cows., Results: Compared with those in healthy cows or controls, apolipoprotein B-100 and A-I concentrations were decreased in cows with ketosis and LDA., Conclusions: Decreases in apolipoprotein B-100 and A-I concentrations in cows with ketosis and LDA indicate that the 2 disorders may be intimately associated with fatty liver., Clinical Relevance: Monitoring of the apolipoprotein B-100 and A-I concentrations during the stages of nonlactation and early lactation is helpful for detecting cows susceptible to ketosis and LDA.

Objective: To compare relative efficacy of dexamethasone and flumethasone alone or in combination with rapid IV infusion of glucose for treatment of ketosis in cattle., Design: Clinical trial., Animals: 127 cows with urine acetoacetate concentration > or = 60 mg/dl., Procedure: Cows were treated with 500 ml of 50% glucose solution. IV, and 40 mg of dexamethasone, IM (group 1), 40 mg of dexamethasone, IM (group 2), 5 mg of flumethasone (group 3), or 500 ml of 50% glucose solution, IV, and 5 mg of flumethasone (group 4). Treatment success was defined as recovery after a single treatment without relapse during the same lactation. Uterine disease (retained placenta or metritis), parity, and pretreatment plasma glucose, serum beta-hydroxybutyric acid, and urine acetoacetate concentrations were evaluated as possible confounding factors affecting recovery., Results: Only uterine disease was found to have a significant effect on recovery. Treatments 1 and 4 were significantly more efficacious than was treatment 2, but efficacy of treatment 2 was not significantly different from that of treatment 3. Regardless of treatment, cows with uterine disease were less likely to have a successful outcome than were cows without uterine disease. In all treatment groups, plasma glucose concentration increased and serum beta-hydroxybutyric acid and urine acetoacetate concentrations decreased following treatment., Clinical Implications: In this study, treatment of ketosis in dairy cattle with a corticosteriod alone was less efficacious than treatment with glucose and a corticosteroid.

Objective: To quantify the effect of season of parturition, parity, and various diseases on time to conception., Design: Event-time analysis (survival analysis)., Sample Population: 44,450 cows delivering calves between September 1985 and September 1986, from 6,227 Ayrshire dairy herds in 80 Finnish communities., Procedures: Primiparous and multiparous cows were analyzed in separate Cox proportional hazards models for postpartum days 56 to 120. Occurrence of 43 diseases or disorders was recorded; codes were condensed into 25 variables offered to each model. Season of parturition was categorized into spring, summer, and fall-winter; for multiparous cows, 3 categorical variables represented parity. Models controlled for 60-day milk and milk fat production, herd milk production, and community. For all observations, parturition-to-conception interval was plotted against calendar day of parturition., Results: For multiparous cows, parturition in the spring or summer and being of parity 2 or 3-4 (vs older) increased the chance of conceiving; 10 diseases or disorders decreased this probability. Similarly, in the model for primiparae, parturition in spring or summer increased the probability of conception, and 6 disorders decreased it. Disorders that were detrimental in both models were anestrus, ovulatory dysfunction, other infertility, late metritis, and clinical ketosis., Conclusions: The effect of season on the parturition-to-conception interval was marked at this latitude. Parturition during late April, causing confluence of postpartum day 55 with the summer solstice, was associated with the shortest parturition-to-conception intervals. Ketosis was found to be an important factor in lengthening the parturition-to-conception interval, highlighting the effect of negative energy balance on postpartum restoration of reproductive function.

Objectives: To investigate in vitro effects of ketosis and hyperglycemia on feline erythrocyte Heinz body formation, reduced glutathione (GSH) concentration, and D- and L-lactate production, and to identify potential metabolic mechanisms of oxidative stress in diabetic cats., Design: Washed feline erythrocytes suspended in buffers containing normal or high glucose concentration were incubated with various concentrations of ketone bodies and tested at defined time intervals for Heinz bodies, GSH concentration, and D- and L-lactate production., Animals: Three healthy female domestic cats., Procedure: Erythrocytes were washed, suspended in buffers containing 5 mM glucose (simulates euglycemia) or 25 mM glucose (simulates hyperglycemia), and incubated with acetone (5 and 10 mM, acetoacetate (5 and 10 mM), or beta-hydroxybutyrate (5 and 25 mM) for 24 hours at 37 C. Aliquots were stained with new methylene blue for Heinz bodies, and assayed spectrophotometrically for GSH and D- and L-lactate concentrations. Experiments were done in triplicate. Data were analyzed, using ANOVA with repeated measures., Results: Neither high glucose concentration nor ketosis had direct effects on Heinz body formation or GSH values. Glutathione decreased to 89% of initial values over the 24-hour period in all samples. High glucose concentration also had no effect on erythrocyte D-lactate production; however, the rate of D-lactate production was slightly increased in samples containing 25 mM beta-hydroxybutyrate. Linear L-lactate production confirmed metabolic viability of the erythrocyte suspensions. Samples in high glucose concentration produced L-lactate at a slightly higher (1.2x) rate than did samples in normal glucose concentration., Conclusions: High glucose concentration and ketosis do not account directly for oxidative damage and glyoxalase induction in feline erythrocytes in vitro, although high concentrations of beta-hydroxybutyrate may stimulate D-lactate formation.

A beef cow was examined to find the cause of decreasing appetite of 2 weeks' duration. The cow was obese (body condition score, 8 of 9), and multiple fetuses were identified on palpation per rectum. Urinalysis revealed > 160 mg of ketones/dl. Abnormal serum biochemical data included high concentrations of bilirubin, creatinine, sodium, and chloride; low concentrations of total CO2 and calcium; and high activity of aspartate transaminase. Treatment included administration of dextrose solution, i.v.; propylene glycol, PO; and insulin, i.v. and SC. The cow's appetite improved gradually over 8 days of treatment. Concentration of ketone bodies in urine decreased to trace amounts by day 4. The cow was discharged on day 10 and gave birth to twins 4 days after discharge (duration of gestation, 279 days). The clinical history of this cow differed from the history of other cattle with ketosis, but mimicked pregnancy toxemia in ewes. Multiple fetuses have not been implicated as a predisposing factor in severe prepartum ketosis of cows.

The association between parturient hypocalcemia and 8 periparturient disorders (dystocia, retained fetal placenta, metritis, left displaced abomasum, foot problems, ketosis, mastitis, and coliform mastitis) was evaluated in 33 Holstein dairy herds (2,190 cows) that calved from March 1981 through February 1982. There were highly significant (P less than 0.0001) associations between parturient hypocalcemia and dystocia, retained fetal placenta, ketosis, and mastitis. The odds ratios (multiplicative increases in occurrence) for these associations were 6.5, 3.2, 8.9, and 8.1, respectively. There was a significantly (P less than 0.03) association between parturient paresis and coliform mastitis (odds ratio, 9.0). There was a tendency for association with left displaced abomasum (odds ratio, 3.4; P less than 0.06).

The effect of toxic or subtoxic concentrations of ketone bodies (acetone, beta-hydroxybutyrate, acetoacetate) in blood on function of bovine lymphocytes was studied in vitro. Lymphocytes separated from peripheral bovine blood were distributed into the wells of Linbro Microtiter plates containing control medium and test medium with various concentrations of ketones and/or phytohemagglutinin. The mitogenic response of lymphocytes was measured by incorporation of [3H]thymidine into DNA of lymphocytes. Toxic and subtoxic concentrations of beta-hydroxybutyrate or the toxic concentration of acetoacetate significantly affected the mitogenic response of bovine lymphocytes. The reduction in the mitogenic response also occurred when lymphocytes were only preincubated for 2 hours or longer with beta-hydroxybutyrate or acetoacetate. The presence of the toxic concentration of acetone in the medium did not affect the mitogenic stimulation of lymphocytes.

Experimental ketosis was induced by feeding calves a diet containing 1,3 butanediol for 9 or 10 days. Blood beta-hydroxybutyrate was significantly (P less than 0.05) elevated during clinical ketosis. The mitogenic response of the lymphocytes collected during ketosis was significantly (P less than 0.01) suppressed, and the suppression persisted for 2 weeks. During ketosis, all calves fed a 1,3 butanediol diet had clinical signs of an upper respiratory tract infection. Possible relationships between the suppressed function of lymphocytes, the increased concentration of 1,3 butanediol, and the increased susceptibility of the calves to infections during ketosis were considered.

Statistical parameters necessary for the comparison of herd blood beta hydroxybutyrate (HB) concentration means with HB concentrations in the general population were determined in 11 clinically normal herds of Holstein-Friesian cows. These parameters were then used to compare clinically normal cows from 2 Holstein-Friesian herds experiencing a high prevalence of clinical ketosis with the normal population. Blood HB concentration means were compared with plasma glucose concentration means for their relative value as predictors of clinical ketosis prevalence within a herd. Blood HB concentration values were distributed approximately log normal and were directly related to amount of milk production. Herds with a high prevalence of clinical ketosis had blood HB log means higher (P less than 0.01) and glucose means lower (P less than 0.05) than did the normal population. Herd blood HB log means should be determined on 7 or more animals within specified production groups. When these means exceed the normal population log mean by more than 1 SD, susceptible cows in the herd may be at increased risk for the development of clinical ketosis. Blood HB log means may be of greater value than are plasma glucose concentration means for the prediction of herd ketosis prevalence.