Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis.

A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.

Biomarkers of liver regeneration allow early prediction of hepatic recovery after acute necrosis.

Acute toxic hepatic necrosis is common and may be fatal. Predicting clinical outcome may be aided by following serum markers that could indicate recovery or may signify massive (substantial) destruction of functional liver mass. Previously, in a published case of chloroform poisoning, we serially assayed serum biomarkers of hepatocellular necrosis (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) and markers of hepatocellular regeneration (alpha-fetoprotein, retinol-binding protein, gamma-glutamyl transferase, and des-gamma-carboxyprothrombin). We noted a decline in necrotic markers and a synchronous elevation in regenerative markers, which could be suggestive of a favorable outcome in similar cases. We now report 6 Amanita mushroom poisonings with favorable outcome and 2 fatal acetaminophen poisonings in which the same markers were observed. Our results further support our hypothesis that a sustained decline in serum markers of hepatocyte necrosis with a concurrent elevation in regenerative markers could aid in prediction of favorable outcome in patients with acute liver injury.

Autologous stem cell transplantation for acute lymphocytic leukemia in adults.

Autologous bone marrow transplantation remains an investigational treatment for adult ALL. Despite many anecdotal studies showing efficacy, the rarity of ALL has prevented the large randomized trials necessary to confirm effectiveness. Candidates for autoBMT include adult patients in first CR with adverse risk factors and all patients who have experienced disease relapse. It remains debatable which preparative regimen is optimal, whether purging is necessary, or if chemotherapy or immunotherapy administered after transplantation can decrease disease relapse. Overall, every effort should be made to enter ALL patients on well-designed randomized multi-institutional trials. These trials should compare autologous transplantation to newer more intensive chemotherapy regimens and should take into account the heterogeneity of ALL. A quality of life analysis should be performed as one high-dose treatment may be less toxic and better tolerated than multiple cycles of consolidation chemotherapy. Strategies aimed at enhancing an autologous graft-versus-leukemia effect after transplantation may enhance long-term survival. Many more studies are needed to further define the optimal role of autoBMT in adult ALL.

Allogeneic stem cell transplantation for acute lymphocytic leukemia in adults.

Acute lymphocytic leukemia remains a difficult disease to treat in adults. Allogeneic bone marrow transplantation can cure some patients with ALL, but GVHD transplant-related mortality and disease relapse remain problematic. Immunotherapeutic approaches aimed at eliminating minimal residual disease and enhancing the GVL effect may decrease relapse rates and improve overall survival. Because of the rarity of this disease in adults, every new patient should be entered in well-designed, peer-reviewed, investigational trial.

Videolaparoscopic treatment for isolated necrosis and abscess of the round ligament of the liver.

A case involving abcess and necrosis of the round ligament of the liver is described. This type of case is seldom reported in medical literature. Laparaoscopy is a very useful and feasible tool for the diagnosis and treatment of such cases. The video shows an oversized round ligament with necrotic appearance partially blocked by the epiplon, gallbladder, and stomach. (This online case report contains a video.).

Role of serum markers for liver function and liver regeneration in the management of chloroform poisoning.

Accidental or intentional chloroform poisoning is rare, but a few such cases have been reported in literature. We report here a successful management of acute chloroform toxicity in a 33-year-old white female who attempted suicide by injecting one half milliliter of chloroform, followed by drinking half a cup the next morning. Plasma chloroform levels, measured by headspace gas chromatography declined rapidly. Sequential measurement of biomarkers in serum for liver cell necrosis, liver function, and liver regeneration indicated the presence of initial liver damage followed by recovery. These results suggest that in addition to biomarkers for liver cell necrosis, serial determinations of markers for liver regeneration provide objective evidence for recovery from chloroform poisoning and possibly other hepatotoxins.

Mature weight, maturation rate, maternal performance and their interrelationships in purebred and crossbred cows of angus and milking shorthorn parentage.

Mature weight, maturation rate and lifetime maternal performance, through a maximum of seven calving seasons, were analyzed for 182 cows of Angus (A) and Milking Shorthorn (S) breeds and the two reciprocal crossbred groups. Mature weight and rate of maturation were estimated for the three-parameter growth curve described by Brody. Estimates derived for mature weight (kilograms), both unadjusted and adjusted for cow condition, were, respectively: Angus, 421, 407; Shorthorn, 409, 459; A x S, 448, 455 and S x A, 440, 441 (approximate standard error, 8 kg). Estimates for the maturation rate parameter were, respectively: Angus, 5.8, 6.3; Shorthorn, 6.6, 5.4, A x S, 6.2, 6.1 and S x A, 5.9, 6.1%/month (approximate SE, .3%/month). Heterosis for mature weight was 3 to 7% (28 +/- 8 and 15 +/- 6 kg, respectively). No heterosis was observed for the maturation rate parameter. Birth weight (.048 +/- .025 kg/kg) and weaning weight (.142 +/- .044 kg/kg) of the first calves were positively related with mature size of the dam. Weaning weights of first calves increased with increasing rate of maturation of the dams (3.6 +/- 1.5 kg/percentage/month) while birth weights remained unchanged. Under the culling criteria used in this study, the number of calves produced by a cow in her lifetime decreased (-.007 +/- .003 calves/kg) with increasing mature weight, while average weaning weight of the calves increased (.132 +/- .03 kg/kg). Total weight weaned, years in the herd and weight weaned per year tended to decrease (P greater than .05) with increasing mature weight of dam, but not significantly. Positive heterosis was expressed for all lifetime cow productivity characters, with crossbred cows weaning 22% (230 +/- 57 kg) more calf weight in their lifetime.

Estimation of genetic and maternal effects in crossbred cattle of Angus, Charolais and Hereford parentage. III. Optimal breed composition of crossbreds.

Methods for estimating genetic and maternal effects in crossbred populations were extended and generalized to allow estimation of optimal breed combinations. Coefficients of the effects were expressed in terms of the probabilities of obtaining genes from a given parental breed through the sire (PiS), dam (PiD) and maternal grandsire (píS). The formulas are applicable to crosses involving any number of breeds. For purposes of graphic presentation, available genetic and maternal parameters for 205-day weight derived from data involving the Angus (A), Charolais (C) and Hereford (H) breeds were used to develop response surfaces for all two-breed combinations of the A, C and H breeds. PiS, PiD and PíS ranged from 0 to 1. In crosses involving varying proportions of the A and C or the H and C breeds, an increased proportion of C genes resulted in increased 205-day weight, and the shape of the performance surface was largely determined by the breed additive effects of the C breed. Individual and maternal heterosis effects influenced the shape of the performance surface of crosses involving varying proportions of A and H. Application of results to the formation of synthetic breeds is discussed.

Growth, development, and carcass composition in five genotypes of swine.

An experiment with 127 barrows representing five genotypes, 1) H x HD, 2) SYN, 3) HD x L[YD], 4) L x YD, and 5) Y x L (H = Hampshire, D = Duroc, SYN = synthetic terminal sire line, L = Landrace, and Y = Yorkshire), was conducted to evaluate growth and development of swine from 59 to 127 kg live weight. Animals were allowed ad libitum access to a pelleted finishing diet containing 18.5% CP, .95% lysine, and 10.5% fat, with an energy density of 3,594 kcal of ME/kg. Pigs were serially slaughtered at either 59, 100, 114, or 127 kg live BW. After slaughter, carcasses were chilled and backfat was measured at four locations. The right side of each carcass was fabricated into primal cuts of ham, loin, Boston Butt, picnic, and belly. Composition of each primal cut was determined by physical dissection into lean, fat, bone, and skin. Estimated allometric growth coefficients for carcass length, carcass weight, and longissimus muscle area relative to BW; carcass lean, fat, bone, and skin relative to both BW and carcass weight; and lean in each of the primal cuts relative to total carcass lean did not differ (P greater than .05) among genotypes. Relative to BW, the pooled growth coefficient(s) for carcass weight was (were) greater (P less than .001) than unity, whereas those for carcass length, longissimus muscle area, and backfat at first rib were smaller (P less than .001) than unity. Those for other backfat measurements were close to 1.00. Relative to either BW or carcass weight, the pooled coefficient(s) for fat was (were) greater (P less than .001) than unity, whereas those for lean, bone, and skin were smaller (P less than .001) than unity. Growth of lean, backfat, bone, and skin in the carcass were nearly linearly associated with increases in BW. The increase in fat weight was curvilinear as the pig grew and was accelerated in later growth stages, indicating that carcass fat percentage increased with increased BW.

Multistage selection for maximum economic return with an application to beef cattle breeding.

Methodology for selection index updating was developed to allow multistage selection. The program determines truncation points for each stage of selection that will maximize either profit or the ratio of aggregate economic gain to cost (R = delta H/C). Either maximum profit or R may be attained by reducing the cost of performance testing in later stages of a multistage program. In order to eliminate the need for multiple integration and assure convergence, a piecewise algorithm was developed. Examples of beef bull selection compared single-stage selection at 1 yr of age, two-stage selection at birth and 1 yr, two-stage selection at 205 d and 1 yr, and three-stage selection at birth, 205 d, and 1 yr. Selection based on three traits (birth weight, gain birth to 205 d, and gain 205 to 365 d) was compared with selection based on four traits (the above three plus ultrasound fat depth) and selection based on five traits (the above four plus feed:gain ratio). Five scenarios were used that allowed variation in proportion of candidates selected for breeding, number of progeny per selected bull, and proportion of profit returned to the nucleus herd. General conclusions based on the examples were 1) multistage selection reduced aggregate economic gain relative to that attained by single-stage selection, 2) inclusion of feed conversion in the index of traits resulted in reduced profit and aggregate economic gain, 3) measurement of feed conversion could be justified when selected bulls produced a large number of progeny, and 4) three-trait selection produced greater profit in all five scenarios than did four- or five-trait selection. Use of the selection updating program described here provides a new source of information that can be used in developing economically sound performance testing and selection programs.

Lifetime productivity of purebred and crossbred cows of Angus and milking shorthorn parentage: weights and scores.

Lifetime productivity of 242 purebred and reciprocal crossbred Angus (A) and Milking Shorthorn (M) cows was studied. Cows were born in the fall during the 5-yr period from 1966 through 1970. Data from each parity, one through six, were analyzed separately by the method of least-squares. The basic statistical model included effects of breed of cow and year of cow birth plus the first-order interaction. Calf weight data were adjusted for effects of sex and calf age. Production stage was included for analyses of cow weights and condition scores. Data from parities seven through 13 were combined in one analysis with the effect of parity added to the model. Appropriate contrasts of estimates of breed means provided estimates of additive, heterotic, maternal and grandmaternal effects. Using pooled averages, crossbred cows were 22.5 kg (5.7%, P less than .01) heavier and .15 condition score units (5.3%, P less than .01) fatter than purebred cows. Condition scores of AM, MA and AA cows were higher (P less than .05) than those of MM cows. Calves from crossbred cows averaged 6.1 and 9.8 kg heavier (4.2 and 4.7%, P less than .01) at 120 and 210 d of age, respectively, than calves from purebred cows. Calves from AM, MA and MM dams were heavier (P less than .05) than those from AA dams. Calf weight at 210 d of age as a percentage of cow weight was used as a measure of efficiency of production. The heterosis contrast was 3.6% (P less than .01), which represented an 8.5% increase of the crossbreds relative to the mean of purebred cows (42.4%).

Reproductive performance of Suffolk and Suffolk-cross ewes and ewe lambs exposed to vasectomized rams before breeding.

Multiparous Suffolk and Suffolk-cross ewes were randomly allotted to treatments within breed and year to measure effects of ram exposure, during transition from anestrus to breeding activity, on reproductive performance. Treatments were: 1) ewes joined with two mature vasectomized Rambouillet rams for 15 d before breeding (DC), 2) ewes maintained across a net wire fence from two vasectomized rams for 15 d before breeding (FC) and 3) ewes maintained approximately 400 m away from rams (NC). At the end of the 15 d, all ewes were placed in one pasture and mated to three fertile Suffolk rams during a 34-d breeding season. A total of 96 Suffolk and 177 Suffolk-cross ewes was utilized during the 3-yr experiment. A greater (P less than .05) prebreeding ovulation percentage was observed in DC and FC than in NC ewes. Mating and lambing occurred approximately 6 d earlier for DC or FC ewes than for NC ewes. A similarly designed experiment was conducted using Suffolk and Suffolk-cross ewe lambs allotted to treatments within breed and year to measure effects of ram exposure during the natural breeding season, but prior to breeding. Treatment differences were not detected (P greater than .05) for date of first observed estrus, date of lambing, percentage of ewes lambing in the first 17 d of the lambing season, number of lambs born per ewe lamb exposed or number of lambs born per ewe lamb giving birth.

Effects of winter and summer energy levels on heifer growth and reproductive performance.

Three heifer development trials were conducted with 337 crossbred heifers (125, 105 and 107 heifers in trials 1, 2 and 3, respectively) over a 3-year period. Heifers were fed low quality fescue hay ad libitum plus 0, 1.22 or 2.45 kg of ground ear corn (GEC) daily during the winter feeding phase of all three trials. Winter gains and final winter and summer condition scores increased (P less than .05) in each trial as winter level of GEC increased. In each trial, summer gains followed the reverse order of winter gains (P less than .05). Conception rate, mean number of days pregnant (as determined by rectal palpation) and adjusted weaning weight of progeny increased linearly with winter level of GEC when pooled over trials. Differences between animals fed 0 and 2.45 kg of GEC were significant. Conception rate and adjusted weaning weight of progeny of the heifers retained in the breeding herd increased (P less than .05) as level of GEC increased when data were pooled over trials. Calving date and percentage live progeny were not significantly affected by winter treatment. Summer daily gains and condition scores were increased by additional summer energy (2.45 kg GEC/day) in trial 3. Conception rate and mean number of days pregnant (conception date) favored heifers given the summer supplementary feeding (2.45 kg GEC) treatment. Among heifers retained in the breeding herd, there were no significant differences between the 0- and 2.45-kg GEC summer treatment groups in conception rate, calving date, percentage live progeny or adjusted weaning weight of progeny.

Genotype and treatment biases in estimation of carcass lean of swine.

Carcasses of 181 barrows, representing five genotypes, 1) H x HD, 2) SYN, 3) HD x L[YD], 4) L x YD, and 5) Y x L (H = Hampshire, D = Duroc, SYN = synthetic terminal sire line, L = Landrace, and Y = Yorkshire), and two levels of ractopamine (RAC) treatment (0 and 20 ppm) were completely dissected and the data were used to examine genotype and treatment (RAC) biases in estimation of fat-standardized lean weight and to evaluate accuracies and precisions realized by use of equations based on variables derived from different technologies. Independent variables used to establish regression equations represented technologies of direct carcass measurements, optical probe data, TOBEC (total body electrical conductivity) readings, and dissected (DHMLN) and fat-standardized (FSHMLN) ham lean. Genotype bias existed when any equation from a single technology was used and was minimized by combining FSHMLN with one TOBEC reading, carcass length, and the probe measurement of 10th rib fat depth. Large RAC biases appeared when equations from direct carcass measurements or optical probe data were used and were minimized by an equation using either DHMLN or FSHMLN. A practical equation with relatively high R2 value and small genotype and RAC biases were developed by combining TOBEC readings with direct carcass measurements of 10th rib fat depth and warm carcass weight.

Lack of a nocturnal rise in serum concentrations of melatonin as gilts attain puberty.

Twenty prepubertal crossbred gilts (Yorkshire x Hampshire x Duroc) weighing 98.1 +/- 4.2 kg at 5 mo of age were placed in an environmentally controlled room having a temperature of 18 degrees C and light:dark cycle of 12 h:12 h. Light intensity measured 700 lx at eye level to the gilts. Three mature ewes were penned adjacent to the gilts to serve as positive controls for the light-dark cycles. After a 30-d acclimation period, 10 gilts from the pool determined to be prepubertal (serum progesterone < 500 pg/mL) were fitted with surgically implanted jugular catheters. Blood samples were drawn at 1100 (4 h after onset of light), 1130, 1200, 2300 (4 h after onset of darkness), 2330, and 2400 for 4 d. On d 5 of sampling, gilts were transported in an open-bed truck for 15 min, returned to their original environment, and exposed to boars for 20 min. Boar exposure was repeated every day throughout the remainder of the experimental period. Blood samples were drawn from each gilt until 7 d after estrus or for 12 d in those gilts that did not exhibit estrus. Blood samples were drawn by venipuncture from the ewes during the entire experimental period. For each sampling day, within an individual gilt or ewe, means of serum concentrations of melatonin (MEL) for night (scotophase) and day (photophase) samples were calculated. After three replications were conducted, four classes of animals were obtained: ewes (n = 9); nonpubertal gilts (n = 10); and two classes of gilts that ultimately reached puberty (prepubertal [n = 16] and postpubertal [n = 16]). Across all gilts, only 65 of 406 bleeding periods (16.0%) had a nocturnal (scotophase) rise in serum MEL. The proportion of gilts expressing a nocturnal rise in serum MEL did not differ as gilts approached puberty (P > .05). Incidence of nocturnal rises of MEL was similar (P > .05) in gilts that attained puberty and gilts that did not attain puberty. Nocturnal rises in MEL were observed in 86.2% of the bleeding periods of ewes housed in the same environment. These data indicate clearly that nocturnal rises in serum MEL are not necessary for a gilt to attain puberty.

Serotonin syndrome due to venlafaxine and maintenance tranylcypromine therapy.

A number of novel serotonergic antidepressants have been introduced to clinical practice over the last decade. These medications are felt to be safe alternatives to the traditional tricyclic antidepressants and monoamine oxidase inhibitors, particularly in the overdose setting. Serious adverse reactions and drug interactions have been appreciated and fatalities have been reported. We describe the development of the serotonin syndrome in a 60 year old female on chronic tranylcypromine treatment following the inadvertent ingestion of a single dose of venlafaxine. Manifestations included and altered mental status that progressed to hyperthermia and coma. She recovered quickly and without complications. Health care providers and poison specialists need to be aware that this potentially serious syndrome can be precipitated by a single dose of a serotonin reuptake inhibitor in patients being treated with a monoamine oxidase inhibitor.

Health and growth performance of barrows reared in all-in/all-out or continuous flow facilities with or without a chlortetracycline feed additive.

OBJECTIVE: To compare health and growth performance in barrows reared in all-in/all-out (AIAO) or continuous flow (CF) management systems. ANIMALS: 400 barrows. PROCEDURE: Barrows (approx 2 months old) were allotted to 4 replications (100 barrows each); barrows were housed in AIAO or CF rooms (10 pens/room), and 50 pigs/replicate received chlortetracycline (CTC, 110 mg/kg of feed). Barrows from each pen were slaughtered at 3, 4, 5, and 6 months old. RESULTS: Barrows in the AIAO room had greater total daily gain (TDG) and lean daily gain (LDG) than did barrows in the CF room. Addition of CTC did not improve TDG or LDG in either environment. Barrows in the AIAO room reached body weight of 104.5 kg in 169.7 days, compared with 177.3 days for barrows in the CF room. Feed-to-gain ratio was not affected by management or CTC. Lungs from barrows reared in AIAO facilities had a lower percentage of lesions than did lungs of barrows reared in CF facilities (1.74% vs 9.52%). Addition of CTC did not affect prevalence and extent of lung lesions. Extent of lung lesions was positively correlated with change in serum optical density (OD) to Mycoplasma hyopneumoniae (r = 0.35), but not with change in serum OD to Actinobacillus pleuropneumoniae. Lean growth and serum OD to M. hyopneumoniae and A. pleuropneumoniae were not correlated. CONCLUSIONS: Health and growth performance were better for barrows in an AIAO facility, compared with a CF facility, but addition of CTC to feed failed to enhance health or performance of barrows in either facility.