Topical Lidocaine or Lidocaine/Diltiazem Ointment Following Rubber Band Ligation of Hemorrhoids: A Prospective 3-Armed Randomized Controlled Trial.

BACKGROUND: Rubber band ligation of hemorrhoids causes less pain than excisional hemorrhoidectomy, but many patients still experience significant postprocedure discomfort. OBJECTIVE: This study aimed to determine whether topical lidocaine, with or without diltiazem, is more effective than placebo for analgesia after hemorrhoid banding. DESIGN: This is a prospective, randomized, double-blinded, placebo-controlled trial. Patients were randomly assigned to 2% lidocaine, 2% lidocaine with 2% diltiazem, or a placebo ointment. SETTINGS: This study was performed at 2 university public teaching hospitals and 2 private hospitals in Australia. PATIENTS: Consecutive patients aged ≥18 years undergoing hemorrhoid banding were selected. INTERVENTIONS: Topical ointments were applied postprocedure 3× daily for 5 days. MAIN OUTCOME MEASURES: Visual analog pain score, opiate analgesia usage, and patient satisfaction were the main outcome measures. RESULTS: Of 159 eligible patients, 99 were randomly assigned (33 in each group). Pain scores were reduced at 1 hour for the lidocaine (OR 4.15 [1.12-15.41]; p = 0.03) and lidocaine/diltiazem groups (OR 3.85 [1.05-14.11]; p = 0.04) compared with placebo. Patients in the lidocaine/diltiazem group had improved satisfaction (OR 3.82 [1.28-11.44]; p = 0.02) and were more likely to recommend the procedure to others (OR 9.33 [1.07-81.72]; p = 0.04). Patients in the lidocaine/diltiazem group required approximately 45% less total and in-hospital analgesia compared with the placebo. There was no difference in complications between any of the groups. LIMITATIONS: A cost/benefit analysis was not performed. Analgesic efficacy appeared to be short term and the procedures were performed only in the hospital/nonambulatory setting. CONCLUSIONS: Topical lidocaine reduced short-term analgesia use, whereas combination lidocaine/diltiazem was associated with both improved analgesia and patient satisfaction after hemorrhoid banding. LIDOCANA TPICA O UNGENTO DE LIDOCANA/DILTIAZEM DESPUS DE LA LIGADURA HEMORROIDAL CON BANDA ELSTICA UN ENSAYO PROSPECTIVO CONTROLADO Y ALEATORIZADO DE TRES BRAZOS: ANTECEDENTES:La ligadura de hemorroides con banda elástica causa menos dolor que la hemorroidectomía escisional, pero muchos pacientes siguen experimentando molestias significativas tras el procedimiento.OBJETIVO:Este estudio tiene como objetivo determinar si la lidocaína tópica, con o sin diltiazem, es más eficaz que el placebo para la analgesia tras la ligadura hemorroidal.DISEÑO:Este es un ensayo prospectivo, aleatorizado, doble ciego, controlado con placebo. Los pacientes fueron aleatorizados para recibir lidocaína al 2 %, lidocaína al 2 % con diltiazem al 2 % o ungüento de placebo.AJUSTES:Este estudio se realizó en dos hospitales públicos con docencia universitaria y dos hospitales privados en Australia.PACIENTES:Se seleccionaron pacientes consecutivos de ≥18 años sometidos a ligadura para hemorroides.INTERVENCIONES:Se aplicaron ungüentos tópicos tras el procedimiento tres veces al día durante 5 días.PRINCIPALES MEDIDAS DE RESULTADO:La puntuación analógica visual del dolor, el uso de analgésicos opiáceos y la satisfacción del paciente fueron las principales medidas de resultado.RESULTADOS:De 159 pacientes elegibles, 99 fueron aleatorizados (33 en cada grupo). Las puntuaciones de dolor se redujeron a la hora para los grupos de lidocaína (OR 4,15 (1,12-15,41); p = 0,03) y lidocaína/diltiazem (OR 3,85 (1,05-14,11), p = 0,04) en comparación con el placebo.Los pacientes del grupo de lidocaína/diltiazem mejoraron su satisfacción (OR 3,82 (1,28-11,44), p = 0,02) y eran más propensos de recomendar el procedimiento a otros (OR 9,33 (1,07-81,72), p = 0,04). Los pacientes del grupo de lidocaína/diltiazem requirieron aproximadamente un 45 % menos de analgesia total e intrahospitalaria en comparación con el grupo de placebo. No hubo diferencia en las complicaciones entre ninguno de los grupos.LIMITACIONES:No se realizó un análisis de costo/beneficio. La eficacia analgésica pareció ser a corto plazo y los procedimientos solo se realizaron en el hospital/entorno no ambulatorio.CONCLUSIÓN:La lidocaína tópica mejora la analgesia a corto plazo, mientras que la combinación de lidocaína/diltiazem se asocia tanto con una mejor analgesia como con la satisfacción del paciente tras la colocación de bandas para hemorroides. (Traducción-Dr Osvaldo Gauto ).

Oncological and clinical outcomes after conventional right hemicolectomy.

PURPOSE: Complete mesocolic excision (CME) has been proposed for better local control of colon cancer and to improve cancer-specific survival (CSS). However, CME may be associated with increased morbidity from bleeding during central vascular ligation. This study aimed to investigate the outcome of conventional right hemicolectomy, a traditional anatomical dissection along anatomical planes with radical excision of the central lymph nodes at the level of the origin of colic artery but without exposure of superior mesenteric vein and artery (SMV/SMA). METHOD: This was a retrospective review of a cohort of all elective right hemicolectomies performed at a specialist tertiary unit during a five-year period (2011-2015). RESULTS: Five-hundred-nineteen patients (271 female, a median age of 73.0 years (interquartile range (IQR) 65.0-80.0)) were included (Stage I disease: 2.7%, stage II: 53.2%, stage III: 33.3%, stage IV: 10.8%). At the latest follow-up (a median 47 months (IQR 29-67)), local recurrence occurred in 34 patients (6.6%). Three-year overall survival was 74.4% and 3-year CSS was 85.9%. Subgroup analysis for stage I-III showed local recurrence in 6.0%, sole distant recurrence in 7.6% while 19 patients (4.1%) suffered concomitant local and distant recurrence. The anastomotic leak rate was 1.0% and perioperative bleeding occurred in 1.2%. CONCLUSIONS: Oncological outcomes comparable to those of CME can be achieved by conventional surgery but with low rates of bleeding complications and anastomotic leakage. The proposed advantages of CME should be carefully considered and balanced against patients' co-morbidities and potential complications.

Accuracy of genomic breeding values in multibreed beef cattle populations derived from deregressed breeding values and phenotypes.

Genomic selection involves the assessment of genetic merit through prediction equations that allocate genetic variation with dense marker genotypes. It has the potential to provide accurate breeding values for selection candidates at an early age and facilitate selection for expensive or difficult to measure traits. Accurate across-breed prediction would allow genomic selection to be applied on a larger scale in the beef industry, but the limited availability of large populations for the development of prediction equations has delayed researchers from providing genomic predictions that are accurate across multiple beef breeds. In this study, the accuracy of genomic predictions for 6 growth and carcass traits were derived and evaluated using 2 multibreed beef cattle populations: 3,358 crossbred cattle of the U.S. Meat Animal Research Center Germplasm Evaluation Program (USMARC_GPE) and 1,834 high accuracy bull sires of the 2,000 Bull Project (2000_BULL) representing influential breeds in the U.S. beef cattle industry. The 2000_BULL EPD were deregressed, scaled, and weighted to adjust for between- and within-breed heterogeneous variance before use in training and validation. Molecular breeding values (MBV) trained in each multibreed population and in Angus and Hereford purebred sires of 2000_BULL were derived using the GenSel BayesCπ function (Fernando and Garrick, 2009) and cross-validated. Less than 10% of large effect loci were shared between prediction equations trained on (USMARC_GPE) relative to 2000_BULL although locus effects were moderately to highly correlated for most traits and the traits themselves were highly correlated between populations. Prediction of MBV accuracy was low and variable between populations. For growth traits, MBV accounted for up to 18% of genetic variation in a pooled, multibreed analysis and up to 28% in single breeds. For carcass traits, MBV explained up to 8% of genetic variation in a pooled, multibreed analysis and up to 42% in single breeds. Prediction equations trained in multibreed populations were more accurate for Angus and Hereford subpopulations because those were the breeds most highly represented in the training populations. Accuracies were less for prediction equations trained in a single breed due to the smaller number of records derived from a single breed in the training populations.

Partial-genome evaluation of postweaning feed intake and efficiency of crossbred beef cattle.

The effects of individual SNP and the variation explained by sets of SNP associated with DMI, metabolic midtest BW, BW gain, and feed efficiency, expressed as phenotypic and genetic residual feed intake, were estimated from BW and the individual feed intake of 1,159 steers on dry lot offered a 3.0 Mcal/kg ration for at least 119 d before slaughter. Parents of these F(1) × F(1) (F(1)(2)) steers were AI-sired F(1) progeny of Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental bulls mated to US Meat Animal Research Center Angus, Hereford, and MARC III composite females. Steers were genotyped with the BovineSNP50 BeadChip assay (Illumina Inc., San Diego, CA). Effects of 44,163 SNP having minor allele frequencies >0.05 in the F(1)(2) generation were estimated with a mixed model that included genotype, breed composition, heterosis, age of dam, and slaughter date contemporary groups as fixed effects, and a random additive genetic effect with recorded pedigree relationships among animals. Variance in this population attributable to sets of SNP was estimated with models that partitioned the additive genetic effect into a polygenic component attributable to pedigree relationships and a genotypic component attributable to genotypic relationships. The sets of SNP evaluated were the full set of 44,163 SNP and subsets containing 6 to 40,000 SNP selected according to association with phenotype. Ninety SNP were strongly associated (P < 0.0001) with at least 1 efficiency or component trait; these 90 accounted for 28 to 46% of the total additive genetic variance of each trait. Trait-specific sets containing 96 SNP having the strongest associations with each trait explained 50 to 87% of additive variance for that trait. Expected accuracy of steer breeding values predicted with pedigree and genotypic relationships exceeded the accuracy of their sires predicted without genotypic information, although gains in accuracy were not sufficient to encourage that performance testing be replaced by genotyping and genomic evaluations.

Genome-wide association study of growth in crossbred beef cattle.

Chromosomal regions harboring variation affecting cattle birth weight and BW gain to 1 yr of age were identified by marker association using the highly parallel BovineSNP50 BeadChip (50K) assay composed of 54,001 individual SNP. Genotypes were obtained from progeny (F(1); 590 steers) and 2-, 3-, and 4-breed cross grandprogeny (F(1)(2) = F(1) x F(1); 1,306 steers and 707 females) of 150 AI sires representing 7 breeds (22 sires per breed; Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental). Genotypes and birth, weaning, and yearling BW records were used in whole-genome association analyses to estimate effects of individual SNP on growth. Traits analyzed included growth component traits: birth weight (BWT), 205-d adjusted birth to weaning BW gain (WG), 160-d adjusted postweaning BW gain (PWG); cumulative traits: 205-d adjusted weaning weight (WW = BWT + WG) and 365-d adjusted yearling weight (YW = BWT + WG + PWG); and indexes of relative differences between postnatal growth and birth weight. Modeled fixed effects included additive effects of calf and dam SNP genotype, year-sex-management contemporary groups, and covariates for calf and dam breed composition and heterosis. Direct and maternal additive polygenic effects and maternal permanent environment effects were random. Missing genotypes, including 50K genotypes of most dams, were approximated with a single-locus BLUP procedure from pedigree relationships and known 50K genotypes. Various association criteria were applied: stringent tests to account for multiple testing but with limited power to detect associations with small effects, and relaxed nominal P that may detect SNP associated with small effects but include excessive false positive associations. Genomic locations of the 231 SNP meeting stringent criteria generally coincided with described previously QTL affecting growth traits. The 12,425 SNP satisfying relaxed tests were located throughout the genome. Most SNP associated with BWT and postnatal growth affected components in the same direction, although detection of SNP associated with one component independent of others presents a possible opportunity for SNP-assisted selection to increase postnatal growth relative to BWT.

Size of ovulatory follicles in cattle expressing multiple ovulations naturally and its influence on corpus luteum development and fertility.

Long-term genetic selection of cattle for fraternal twins has increased the frequency of twin and triplet ovulations. In contrast, the ratio of fetal numbers to ovulation sites in pregnant females with twin (0.83) or triplet (0.73) ovulations is <1.0 and the number of calves per parturition is 1.6 and 2.0, respectively. Failure of individual twin or triplet ovulations to yield a conceptus in fertile females indicates a significant contribution of ovulation or oocyte anomalies to increased fertilization failure or early embryonic mortality. The present objective was to identify physiological traits affecting conception in cyclic cattle expressing multiple ovulations naturally, including the effect of ovulation rate on follicle or corpus luteum (CL) size, and their relationship to conception. Diameter of the individual ovulatory follicles was measured by transrectal ultrasonography at AI and ranged from 8 to 30 mm, with a trend for diameter of the individual follicles, and associated CL, to decrease with increasing ovulation rate. Independent of ovulation rate, ovulatory follicles were smaller (P < 0.05) for nulliparous heifers (1.5 yr) compared with parous cows (> or =2.5 yr). Pregnancy and fetal status were diagnosed by transrectal ultrasonography between 42 and 72 d after AI. Fertility was reduced (P < 0.01) for small twin or triplet ovulatory follicles (8 to 8.9 mm vs. 10 to 17.9 mm diam.), whereas fertility in monovular females was reduced (P < 0.01) for large ovulatory follicles (> or =22 vs. 14 to 17.9 mm). Plasma progesterone concentrations increased with ovulation rate and were correlated positively with total CL or ovulatory follicle volume per female, indicating that CL size and function were influenced by the size of the follicle of origin. Progesterone was greater (P < 0.05) in the blood of nulliparous heifers compared with parous cows. The increased proportion of small ovulatory follicles associated with twin and triplet ovulations indicates that some ovulatory follicles were either selected to ovulate at a lesser stage of maturity or rescued while undergoing atresia, thus compromising oocyte competency or ovulation. Of greatest importance for reduced fertility was the greater incidence of pregnancy losses occurring in the middle of gestation in females gestating 2 or more fetuses as an apparent effect of uterine crowding, especially when 2 or more fetuses were contained within 1 uterine horn.

Evaluation of antral follicle count and ovarian morphology in crossbred beef cows: investigation of influence of stage of the estrous cycle, age, and birth weight.

Depletion of the ovarian reserve is associated with reproductive senescence in mammalian females, and there is a positive relationship between the size of the ovarian reserve and the number of antral follicles on the surface of the ovary. Therefore, we conducted a series of experiments to investigate the influence of stage of the estrous cycle, age, and birth weight on antral follicle counts (AFC) in beef cows and heifers. Pairs of ovaries were collected from crossbred beef cows at slaughter (n = 72) or at necropsy (n = 333; 0 to 11 yr of age); all visible antral follicles were counted, the ovaries were weighed, and stage of the estrous cycle was estimated based on ovarian morphology. There was no influence of estimated stage of the estrous cycle on AFC (P = 0.36). There was a small but positive effect of birth weight on AFC [AFC = -1.7 + 0.31(birth weight); P = 0.007, r(2) = 0.05]. When antral follicle counts were regressed on age, there was a quadratic effect of age such that AFC increased until 5 yr of age and decreased thereafter [AFC = 12.9 + 9.0(yr) - 0.86(yr(2)); P < 0.001, r(2) = 0.22]. In a third experiment, crossbred beef heifers (n = 406; 353 to 463 d of age) at 3 locations were subjected to ovarian ultrasonography on unknown day of the estrous cycle. Heifers were classified as low AFC (<15 follicle, n = 84) or high AFC (>24 follicles, n = 178). Whereas estimated stage of the estrous cycle did not influence AFC (P = 0.62), heifers classified as low AFC had smaller ovaries (P = 0.001), decreased birth weight (P = 0.003), and a decreased heifer pregnancy rate (P = 0.05) compared with heifers in the high AFC group. From these results, we conclude that AFC in beef cows and heifers is influenced by birth weight and age but not by stage of the estrous cycle. In beef cows, the number of antral follicles increases to 5 yr of age and then begins to decline. This may indicate that a decrease in fertility due to decline of the ovarian reserve may begin earlier than previously thought in beef cows.

Confirmation of quantitative trait loci using a low-density single nucleotide polymorphism map for twinning and ovulation rate on bovine chromosome 5.

Traditional genetic selection in cattle for traits with low heritability, such as reproduction, has had very little success. With the addition of DNA technologies to the genetic selection toolbox for livestock, the opportunity may exist to improve reproductive efficiency more rapidly in cattle. The US Meat Animal Research Center Production Efficiency Population has 9,186 twinning and 29,571 ovulation rate records for multiple generations of animals, but a significant number of these animals do not have tissue samples available for DNA genotyping. The objectives of this study were to confirm QTL for twinning and ovulation rate previously found on BTA5 and to evaluate the ability of GenoProb to predict genotypic information in a pedigree containing 16,035 animals when using genotypes for 24 SNP from 3 data sets containing 48, 724, or 2,900 animals. Marker data for 21 microsatellites on BTA5 with 297 to 3,395 animals per marker were used in conjunction with each data set of genotyped animals. Genotypic probabilities for females were used to calculate independent variables for regressions of additive, dominance, and imprinting effects. Genotypic regressions were fitted as fixed effects in a 2-trait mixed model analysis by using multiple-trait derivative-free REML. Each SNP was analyzed individually, followed by backward selection fitting all individually significant SNP simultaneously and then removing the least significant SNP until only significant SNP were left. Five significant SNP associations were detected for twinning rate and 3 were detected for ovulation rate. Two of these SNP, 1 for each trait, were significant for imprinting. Additional modeling of paternal and maternal allelic effects confirmed the initial results of imprinting done by contrasting heterozygotes. These results are supported by comparative mapping of mouse and human imprinted genes to this region of bovine chromosome 5.

Opportunities for collaborative phenotyping for disease resistance traits in a large beef cattle resource population.

The Germplasm Evaluation (GPE) Project at the US Meat Animal Research Center (USMARC) is planned to produce about 3,000 calves per year in support of the following objectives: identification and validation of genetic polymorphisms related to economically relevant traits (ERT), estimation of breed and heterosis effects among 16 breeds for ERT, and estimation of genetic correlations among ERT and physiological indicator traits (PIT). Opportunities exist for collaboration in the development and collection of PIT phenotypes for disease resistance. Other areas of potential collaboration include detailed diagnosis (identification of disease causing organisms, etc.) of treated animals, collaborative development of epidemiological statistical models that would extract more information from the records of diagnoses and treatments, or pharmacogenetics. Concentrating a variety of different phenotypes and research approaches on the same population makes each component much more valuable than it would be individually.

Present and future applications of DNA technologies to improve beef production.

Substantial improvements in production efficiency and quality of beef and dairy products have been made possible through manipulation of bovine genetics. The advent of modern breeds in the last two centuries, the institution of phenotypic selection practices and quantitative genetics, even the process of domestication in the distant past, have all represented means to make use of naturally occurring variation in the genome to tailor the animal for a desired outcome. We discuss the history of genome research in cattle and recent technological advances that promise a leap forward in the use of DNA sequence to facilitate selection, in which a detailed genome-level view for individual animals may provide comprehensive and relatively accurate assessment of the consequences, both desired and unintended, of genetic selection for livestock production.

Increased calf production in cattle selected for twin ovulations.

The effects of increasing fetal numbers and their distribution between the left and right uterine horns on calf survival, calf BW at birth and weaning, gestation length, dystocia, and calf sex ratio were evaluated for single (n = 1,587), twin (n = 2,440), and triplet calves (n = 147) born to primiparous and multiparous females in the Twinner population at the US Meat Animal Research Center between 1994 and 2004. Cattle were distributed equally between the spring and fall breeding seasons. Fetal number and distribution in utero were determined by real-time ultrasonography at 40 to 70 d postbreeding. For cows and heifers combined, number of calves per parturition increased from 1.34 in 1994 to 1.56 in 2004. Gestation length was 6.8 d shorter (P < 0.01) for twins compared with singles (277.5 +/- 0.2 vs. 284.3 +/- 0.2 d) and 12.7 d shorter for triplets (271.6 +/- 0.8 d). Survival and BW of individual calves at birth decreased (P < 0.01) but total calf BW per dam increased (P < 0.01) as fetal number increased from single to triplet births. Twins resulting from bilateral twin ovulations had increased (P < 0.01) survival and BW at birth, a longer (P < 0.01) gestation length, and less (P < 0.01) dystocia than twins resulting from unilateral twin ovulations. Calf survival and BW at birth were 97.2 +/- 0.3% and 48.0 +/- 0.1 kg for singles, 92.0 +/- 0.4% and 39.0 +/- 0.2 kg for bilateral twins, 83.2 +/- 0.4% and 36.7 +/- 0.2 kg for unilateral twins, 73.8 +/- 1.4% and 30.6 +/- 0.7 kg for bilateral triplets, and 51.9 +/- 3.2% and 31.7 +/- 1.6 kg for unilateral triplets. Birth weight of single calves increased by 0.51 kg/d for each additional day of gestation length vs. 0.38 kg/d for individual twins. Calf BW at birth increased (P < 0.01) with age of dam from 2 to 4 yr. Twin and triplet births had a greater (P < 0.01) incidence of dystocia than single births. The ratio of male:female calves (0.52:0.48) at birth was not affected by type of birth. Postnatal calf survival was similar for all 3 types of birth. Total progeny BW at weaning for single, twin, and triplet births was 217.7 +/- 2.5, 328.3 +/- 3.2, and 378.4 +/- 15.0 kg, respectively (P < 0.01). Although most bovine females have the uterine capacity to gestate twin calves, decreased survival and BW of unilateral twins and of all triplets indicate that their growth and development may have been compromised by uterine crowding.

Effects of ovulation rate and fetal number on fertility in twin-producing cattle.

Effects of ovulation rate and of fetal number and distribution within the uterus on pregnancy rate and fetal survival were evaluated in nulliparous (n = 1,331) and parous (n = 3,517) cattle selected for twinning. Cattle were divided into a spring (70 d) and fall (60 d) breeding season and bred by a combination of AI and natural service. Ovulation rate, pregnancy status, and fetal number and distribution were determined by transrectal, real-time ultrasonography of the uterus and both ovaries at the end of the breeding season. Pregnancy was reconfirmed by rectal palpation at 75 to 135 d of gestation. For heifers and cows combined, ovulation rate increased (P < 0.01) from 1.46 +/- 0.4 in 1994 to 1.89 +/- 0.4 in 2004; number of calves per parturition increased (P < 0.01) from 1.34 +/- 0.3 to 1.56 +/- 0.3, respectively, which included an increase in triplet and quadruplet ovulations and triplet births. Bilateral twin ovulations yielded proportionately more (P < 0.01) twin births than unilateral twin ovulations. Ovulation rate was greater (P < 0.01) in the fall than spring breeding season. Pregnancy rate at ultrasound diagnosis did not differ among females with 1, 2, or 3 ovulations (89.1 +/- 0.7, 91.2 +/- 0.7, or 91.5 +/- 2.8%, respectively), but rates at calving decreased (P < 0.01) with increasing ovulation rate (85.1 +/- 0.6, 82.7 +/- 0.6, or 64.2 +/- 2.7%, respectively). Pregnancy rate was less (P < 0.01) after twin or triplet births than single births. For dams birthing twins or triplets, pregnancy rate was less in the fall vs. spring, but rates were similar between seasons for dams with a single birth (type of birth x season, P < 0.05). Cows 60 d, regardless of type of birth. Maintenance of pregnancy to term differed (P < 0.01) among females diagnosed with 1, 2, or 3 fetuses (95.7 +/- 0.6, 87.8 +/- 0.8, and 54.9 +/- 2.3%, respectively). The reduced survival of twin and triplet fetuses in heifers had occurred (P < 0.01) by d 75 to 135 of gestation, and fetal losses were greater (P < 0.01) for unilateral than bilateral twins or triplets, whereas loss of twin or triplet fetuses in cows occurred later in gestation, and losses were not affected by uterine location. Thus, increased calf production from selecting for increased ovulation rate in beef cattle is tempered by increased fetal mortality, partially associated with the crowding of 2 or 3 fetuses within 1 uterine horn, especially in heifers.