Variation in descriptors of patient characteristics in randomized clinical trials of peptic ulcer repair: a systematic review.

BACKGROUND: The ability to compare findings across surgical research is important. Inadequate description of participants, interventions or outcomes could lead to bias and inaccurate assessment of findings. The aim of this study was to assess consistency of description of participants using studies comparing laparoscopic and open repair of peptic ulcer as an example. METHODS: This systematic review is reported in line with the PRISMA checklist. Searches of MEDLINE and Embase databases were performed to identify studies comparing laparoscopic and open repair of perforated peptic ulcer in adults, published in the English language. Manuscripts were dual-screened for eligibility. Full texts were retrieved and dual-screened for inclusion. Data extracted from studies included descriptors of participants in studies from tables and text. Descriptors were categorized into conceptual domains by the research team, and coverage of each domain by study was tabulated. RESULTS: Searches identified 2018 studies. After screening, 37 full texts were retrieved and 23 studies were included in the final synthesis. A total of 76 unique descriptors were identified. These were classified into demographics (11 descriptors), vital signs (9 descriptors), disease-specific characteristics (10 descriptors), presentation and pathway factors (4 descriptors), risk factors (8 descriptors), laboratory tests (14 descriptors) and baseline health (28 descriptors). The number of descriptors in a single study ranged from three to 31. All studies reported at least one demographic descriptor. Laboratory tests was the least frequently described domain. CONCLUSION: Study participants are described inconsistently in studies of a single example surgical condition.

ANTECEDENTES: La capacidad de comparar los hallazgos en la investigación quirúrgica es importante. Una descripción inadecuada de los participantes, las intervenciones o los resultados podría conllevar sesgos y una evaluación incorrecta de los hallazgos. El objetivo de este estudio fue evaluar la consistencia en la descripción de los participantes utilizando los estudios comparativos de la cirugía laparoscópica con la cirugía abierta en el tratamiento de la úlcera péptica, como modelo. MÉTODOS: Esta revisión sistemática se presenta de acuerdo con la lista de verificación PRISMA. Se realizaron búsquedas en las bases de datos MEDLINE y EMBASE para identificar estudios, publicados en inglés, que compararan el tratamiento quirúrgico laparoscópico y abierto de la úlcera péptica perforada en adultos. Los artículos elegibles fueron sometidos a un doble cribaje para su selección. Se recuperaron los textos completos de los artículos y se evaluaron por partida doble para su inclusión. Los datos extraídos correspondían a los términos que describían las poblaciones de estudio en el texto y en las tablas de los artículos. Dichos términos descriptores fueron clasificados por el equipo de investigación en dominios conceptuales, registrándose la cobertura de cada dominio en cada estudio. RESULTADOS: Las búsquedas bibliográficas identificaron 2.018 estudios. Después de la selección, se recuperaron 37 artículos de texto completo y se incluyeron 23 estudios en la síntesis final. Se identificaron un total de 76 descriptores únicos. Dichos descriptores se clasificaron en demográficos (11 variables), signos vitales (9 variables), características específicas de la enfermedad (10 variables), factores de presentación y del proceso (4 variables), factores de riesgo (8 variables), pruebas de laboratorio (14 variables) y estado de salud basal (28 variables). El número de descriptores en un solo estudio varió de 3 a 31. Todos los estudios presentaron al menos un descriptor demográfico. Las pruebas de laboratorio fueron el dominio descrito con menor frecuencia. CONCLUSIÓN: Esta revisión demuestra que los participantes en los estudios se describen de manera inconsistente, tras haber tomado como modelo los estudios de una sola patología quirúrgica.

Excess adiposity and gastrointestinal cancer.

BACKGROUND: Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice. METHODS: Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention. RESULTS AND CONCLUSION: A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future.

The role of cholecystectomy following endoscopic sphincterotomy and bile duct stone removal.

INTRODUCTION: Choledocholithiasis is common, with patients usually treated with endoscopic retrograde cholangiopancreatography (ERCP) and subsequent cholecystectomy to remove the presumed source of common bile duct (CBD) stones. However, previous investigations into the management of patients following ERCP have focused on recurrent CBD stones, negating the risks of cholecystectomy. This article appraises the role of cholecystectomy following successful endoscopic clearance of bile duct stones. METHODS: Patients undergoing ERCP and CBD clearance for choledocholithiasis at St James's University Hospital January 2015-December 2018 were included. Patients were divided into those who received cholecystectomy and those managed non-operatively. Readmissions, operative morbidity, mortality and treatment costs were investigated. RESULTS: Eight hundred and forty-four patients received ERCP and CBD clearance with 3.9 years follow-up. Two hundred and nine patients underwent cholecystectomy with 15% requiring complex surgery. Three hundred and seventy-three patients were non-operatively managed. Unplanned readmissions occurred in 15% following ERCP, mostly within two years. There was no difference in readmissions between the two groups. Accounting for the entire patient pathway, non-operative management was less expensive. CONCLUSIONS: The majority of patients do not require readmission following ERCP for CBD stones, and cholecystectomy did not reduce the risk of readmission. Few patients have recurrent CBD stones, but complex biliary surgery is frequently required. Routine cholecystectomy following ERCP needs to be re-evaluated and a more stratified approach to future risk developed.

Hepatic steatosis in patients undergoing resection of colorectal liver metastases: A target for prehabilitation? A narrative review.

The prevalence of elevated intra-hepatic fat (IHF) is increasing in the Western world, either alone as hepatic steatosis (HS) or in conjunction with inflammation (steatohepatitis). These changes to the hepatic parenchyma are an independent risk factor for post-operative morbidity following liver resection for colorectal liver metastases (CRLM). As elevated IHF and colorectal malignancy share similar risk factors for development it is unsurprisingly frequent in this cohort. In patients undergoing resection IHF may be elevated due to excess adiposity or its elevation may be induced by neoadjuvant chemotherapy, termed chemotherapy associated steatosis (CAS). Additionally, chemotherapy is implicated in the development of inflammation termed chemotherapy associated steatohepatitis (CASH). Following cessation of chemotherapy, patients awaiting resection have a 4-6 week washout period prior to resection that is a window for prehabilitation prior to surgery. In patients with NAFLD dietary and pharmacological interventions can reduce IHF within this timeframe but this approach to modifying IHF is untested in this population. In this review, the aetiology of CAS and CASH is reviewed with recommendations to identify those at risk. We also focus on the post-chemotherapy washout period, reviewing dietary interventions applied to the metabolic population and suggest this window may be used as an opportunity to optimise IHF with such a regime as part of a pre-operative prehabilitation programme to produce improved patient outcomes.

Digital histology quantification of intra-hepatic fat in patients undergoing liver resection.

BACKGROUND: High intra-hepatic fat (IHF) content is associated with insulin resistance, visceral adiposity, and increased morbidity and mortality following liver resection. However, in clinical practice, IHF is assessed indirectly by pre-operative imaging [for example, chemical-shift magnetic resonance (CS-MR)]. We used the opportunity in patients undergoing liver resection to quantify IHF by digital histology (D-IHF) and relate this to CT-derived anthropometrics, insulin-related serum biomarkers, and IHF estimated by CS-MR. METHODS: A reproducible method for quantification of D-IHF using 7 histology slides (inter- and intra-rater concordance: 0.97 and 0.98) was developed. In 35 patients undergoing resection for colorectal cancer metastases, we measured: CT-derived subcutaneous and visceral adipose tissue volumes, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), fasting serum adiponectin, leptin and fetuin-A. We estimated relative IHF using CS-MR and developed prediction models for IHF using a factor-clustered approach. RESULTS: The multivariate linear regression models showed that D-IHF was best predicted by HOMA-IR (Beta coefficient(per doubling): 2.410, 95% CI: 1.093, 5.313) and adiponectin (ß(per doubling): 0.197, 95% CI: 0.058, 0.667), but not by anthropometrics. MR-derived IHF correlated with D-IHF (rho: 0.626; p = 0.0001), but levels of agreement deviated in upper range values (CS-MR over-estimated IHF: regression versus zero, p = 0.009); this could be adjusted for by a correction factor (CF: 0.7816). CONCLUSIONS: Our findings show IHF is associated with measures of insulin resistance, but not measures of visceral adiposity. CS-MR over-estimated IHF in the upper range. Larger studies are indicated to test whether a correction of imaging-derived IHF estimates is valid.

Synthesis and antiviral activity of some 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides.

The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride (DAST). Removal of the 2'-O-protecting group from 26a and subsequent reaction with DAST furnished the 2'-deoxy-2'-fluoro-beta-D-ribo-pentofuranosyl nucleoside 29. Selective fluorination with DAST of the 5'-O-protected analogues 3'-deoxy-3'-C-hydroxymethyl derivatives 13a and 13b gave the 3'-deoxy-3'-C-fluoromethyl derivatives 30a and 30b, while nonselective fluorination afforded the 2',3'-dideoxy-2'-fluoro-3'-C-fluoromethyl analogues 31a and 31b. The deprotected uracil analogue 17a was iodinated to the 5-iodouracil derivative 18. The fully deprotected fluorinated 3'-C-branched nucleosides 14-18 and 32 were evaluated for their antiviral activity. None were active against human immunodeficiency virus type-1 (HIV-1) at concentrations up to 100 microM. However, 5-iodouracil analogue 18 showed activity, comparable to that of acyclovir, against varicella zoster virus without observed cytotoxicity.

Synthesis and antiviral activity of 3'-deoxy-3'-C-hydroxymethyl nucleosides.

A series of 3'-branched-chain sugar nucleosides, in particular 3'-deoxy-3'-C-hydroxmethyl nucleosides, have been synthesized and evaluated as antiviral agents. Reaction of 1-(2,3-epoxy-5-O-trityl-beta-D-lyxo-pentofuranosyl) derivatives 12 and 13, of uracil and thymine, respectively, with 5,6-dihydro-2-lithio-5-methyl-1,3,5-dithiazine 14 afforded the corresponding 3'-functionalized nucleosides 15 and 16, respectively. Replacement of the trityl group with tertbutyldiphenylsilyl allowed high yielding hydrolysis of the 3'-function to give the 3'-deoxy-3'-C-formyl-beta-D-arabino-pentofuranosyl nucleosides 21 and 22. Desilylation afforded the 1-(3-deoxy-3-C-formyl-beta- D-lyxo-pentofuranosyl) 3',5'-O-hemiacetal nucleosides 33 and 34, respectively. Reduction of the formyl group of 21 and 22, followed by desilylation, yielded the 3'-deoxy-3'-C-(hydroxymethyl)-beta-D-arabino- pentofuranosyl) analogues 7 and 8, respectively. The uracil base moiety of 7 was converted to 5-iodouracil and then to (E)-5-(2-bromovinyl)uracil to furnish an analogue 10 of BVaraU. The 1-(3-deoxy-3-C-(hydroxymethyl)-beta-D-lyxo-pentofuranosyl) and 1-(2,3-dideoxy-3-C-(hydroxymethyl)-beta-D-erythro-pentofuranosyl) derivatives of uracil (31 and 6, respectively) and 5-iodouracil (32 and 9, respectively) were also obtained. All novel, fully deprotected nucleoside analogues were evaluated for antiviral activity against human immunodeficiency virus type-1, herpes simplex virus types-1 and -2, varicella zoster virus, human cytomegalovirus and influenza A. Of the compounds tested only (E)-5-(2-bromovinyl)-1-[3-deoxy- 3-C-(hydroxymethyl)-beta-D-arabino-pentofuranosyl]uracil (10) inhibited VZV (alone), but did so at concentrations well below the cytotoxicity threshold.

The synthesis and antiviral activity of some 4'-thio-2'-deoxy nucleoside analogues.

Starting from benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro- pentofuranoside (4), the following 2'-deoxy nucleoside analogues have been synthesized: 4'-thiothymidine (8), 3'-azido-4'-thio- deoxythymidine (10), and (E)-5-(2-bromovinyl)-4'-thio-2'-deoxyuridine (22). The first compound is toxic, the second is not toxic nor has detectable biological activity, and the third is not toxic and has significant activity against some herpesviruses.

Fluorinated analogues of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea: an attempt to control metabolism.

In seeking to block and thereby determine the role of the rapid in vivo hydroxylation of the cyclohexyl moiety of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in relation to antitumor activity and tissue distribution, the 3-(1H-decafluorocyclohexyl) analogue (FCCNU) was synthesized. FCCNU showed marked toxicity and little activity against the intracerebral L1210 leukemia in mice. At pH 7 in phosphate buffer at room temperature FCCNU rapidly decomposed to give 1-(1H-decafluorocyclohexyl)-3-nitrosoimidazolidin-2-one (3) and thence, by loss of HF, the 1-(nonafluorocyclohexenyl) derivative (4); CCNU did not follow this decomposition pathway to any significant extent. Both 3 and 4 were unstable in the buffer, but each was isolated crystalline and characterized. The formation of 3 and 4 account for the biological properties of FCCNU.

Synthesis and biological evaluation of some cyclic phosphoramidate nucleoside derivatives.

(E)-5-(2-Bromovinyl)-2'-deoxy-5'-O-(3-methyl-2-oxo-5-formyl-1,3,2- oxazaphosphacyclopentan-2-yl)uridine has been synthesized and, under physiological conditions and without the necessity for enzyme activity, has been shown to yield the 5'-nucleotide in vitro. Unfortunately this compound is not sufficiently stable in solution for it to be tested in vivo. The biological properties of this and some related derivatives of (E)-5-(2-bromovinyl)-2'-deoxyuridine and acyclovir have been evaluated in in vitro and in vivo systems designed to show the effects of any intracellular liberation of the nucleotide. Although some of the derivatives are probably acting as prodrugs of the active nucleosides, there is no evidence for the liberation of meaningful concentrations of the 5'-nucleotide by any of the compounds.

Synthesis and antiviral properties of some 2'-deoxy-5-(fluoroalkenyl)uridines.

The following 5-substituted 2,4-dimethoxypyrimidines were synthesized: 5-(2,2,2-trichloro-1-hydroxyethyl), 5-(2,2,2-trichloro-1-fluoroethyl),5-(2,2-dichloro-1-fluorovinyl) (5), and 5-(perfluoropropen-1-yl) (a mixture of E and Z isomers, 6 and 7). Demethylation of 5 gave 5-(2,2-dichloro-1-fluorovinyl)uracil, and demethylation of the mixture of 6 and 7 gave some pure (E)-5-(perfluoropropen-1-yl)uracil. Compound 5 was converted into its 2'-deoxyribonucleoside (12) and its alpha-anomer by standard procedures. 2'-Deoxy-3,5-dilithio-3',5'-O-bis(trimethylsilyl)uridine was reacted with the appropriate fluoroalkene to give the following 5-substituted 2'-deoxyuridines in low yield (6-24%): 5-(2-chloro-1,2-difluorovinyl) (a mixture of E and Z isomers, 15 and 16, which were separated on a small scale), 5-(perfluoropropen-1-yl), 5-(perfluorocyclohexen-1-yl), and 5-(perfluorocyclopenten-1-yl). In these reactions, 2'-deoxy-5-(trimethylsilyl)uridine and 2'-deoxyuridine were also formed. The 5-substituted 2'-deoxyuridines were tested for activity against herpes simplex virus type 1. Compound 12 and the mixture of 15 and 16 had an ID50 of 20-26 micrograms/mL in Vero cells. The activity of the mixture resided in one isomer, which by analogY with the corresponding (Z)- and (E)-5-(2-bromovinyl)-2'-deoxyuridines was concluded to be the Z isomer (16).

Synthesis and anti-herpes virus activity of 2'-deoxy-4'-thiopyrimidine nucleosides.

A series of 5-substituted 2'-deoxy-4'-thiopyrimidine nucleosides was synthesized and evaluated as potential antiviral agents. A number of analogues such as 2'-deoxy-5-propyl-4'-thiouridine (3ii), 2'-deoxy-5-isopropyl-4'-thiouridine (3iii), 5-cyclopropyl-2'-deoxy-4'-thiouridine (3iv), 2'-deoxy-4'-thio-5-vinyluridine (3viii), and 5-(2-chloroethyl)-2'-deoxy-4'-thiouridine (3xx) were found to be highly active against herpes simplex virus type-1 (HSV-1) and varicella zoster virus (VZV) in vitro with no significant cytotoxicity. The compound with the broadest spectrum of activity was 2'-deoxy-5-ethyl-4'-thiouridine (3i) which showed significant activity against HSV-1, HSV-2, and VZV.

Pharmacokinetic basis for the comparative antitumour activity and toxicity of chlorambucil, phenylacetic acid mustard and beta, beta-difluorochlorambucil (CB 7103) in mice.

This report describes the relationship between the pharmacokinetics, antitumour activity and toxicity of chlorambucil (CHL), phenylacetic acid mustard (PAAM) and beta, beta-difluorochlorambucil (beta-F2CHL) in mice. Pharmacokinetics were studied by HPLC, antitumour activity by a regrowth delay assay using the KHT murine sarcoma and toxicity by acute LD50. For both antitumour activity and acute toxicity the order of potency was: PAAM greater than CHL greater than beta-F2CHL. CHL and PAAM exhibited identical therapeutic indices, whereas that for beta-F2CHL was somewhat improved. CHL is metabolized by mitochondrial beta-oxidation to the 3,4-dehydro derivative (DeHCHL) and PAAM, and the latter is further metabolized to its monodechloroethylated derivative DeC-PAAM, presumably by hepatic microsomal enzymes. Administered PAAM gave only one metabolite, DeC-PAAM. Unexpectedly, despite beta, beta-disubstitution, beta-F2CHL was also beta-oxidized to give DeHCHL and PAAM, but at reduced rates. Further, metabolic switching was demonstrated with the appearance in large amount of 2 new, unidentified metabolites, which may be dechlorethylation products. The pharmacokinetics of administered CHL, PAAM and beta-F2CHL differ in that the plasma clearance was fastest for CHL, slowest for PAAM and intermediate for beta-F2CHL. For the metabolites, CHL produced peak plasma concentrations of DeHCHL and PAAM, respectively, 7-fold and 2-fold greater than those produced by beta-F2CHL. However, despite these differences, exposures to total bifunctional nitrogen mustards were similar following administration of the 3 drugs and therefore cannot account for their differential activity. In contrast, there was a good correlation between potency and PAAM exposure, which is highest after treatment with PAAM, intermediate after CHL and lowest after beta-F2CHL. In plasma, 3.2% of PAAM is present as nonprotein-bound free drug, compared to 1.3% for DeHCHL, 0.9% for CHL and 0.45% for beta-F2CHL. We propose the amount of free bifunctional nitrogen mustard, itself partly dependent on the extent of metabolism, to be of major importance for the in vivo potency of CHL analogues.

Differences in bull spermiograms using eosin-nigrosin stain, feulgen stain, and phase contrast microscopy methods.

The Society for Theriogenology recently adopted a minimum standard of 70% normal spermatozoa for the bull breeding soundness examination (BSE). We conducted this study to determine if spermiograms derived by brightfield microscopy of eosin-nigrosin stained semen smears (Society method) overestimated the proportion of normal spermatozoa. Comparison of the above method was made with that of phase contrast microscopy (Phase method). We then evaluated our ability to discern head abnormalities by comparing brightfield microscopy of Feulgen-stained sperm DNA (Feulgen method) with those of the Society and Phase methods. Spermiograms were determined for each of the 181 beef bulls using all 3 methods. Only bulls that were being routinely tested prior to the 1993 breeding season were included. The mean percentage of normal spermatozoa surpassed the minimum standard with the Society (72.8%) but not the Phase (52.5%) method, which identified more distal cytoplasmic droplets that adhered to cells without distal midpiece reflexes. The Phase method also identified more total primary and fewer primary head abnormalities. We conclude that the Phase method is not a suitable substitute for the Society method when applying the minimum standard during a routine BSE. The Feulgen method identified more head abnormalities, especially in the pattern of DNA, than the other methods, however, when compared to the minimum standard that improvement was not clinically important. Both the Phase and Feulgen methods are better than the Society method for monitoring changes in abnormal spermiograms over time.

Adjusted 200-day scrotal size as a predictor of 365-day scrotal circumference.

Data collected from 264 bulls of 13 beef breeds at the Michigan Bull Test Station was evaluated to determine if scrotal circumference (SC) adjusted to 200 d of age could be used to predict scrotal circumference at 1 yr of age. Scrotal circumference of each bull was recorded on arrival at the test station and at the time of breeding soundness examination (BSE) and was adjusted to 200 and 365 d of age, respectively. Bulls with adjusted SC>34.0 cm by 365 d of age averaged a larger SC at 200 d (P < 0.0001) and faster scrotal growth (P < 0.0001) than bulls with a 365 d adjusted SC /= 23.0 cm had a 95% probability of achieving SC > 34.0 cm by one year of age. Calves measuring < 23 cm at 200 d had a 54% probability of achieving > 34.0 cm scrotal size by one year. This information can contribute to the selection of breeding bulls that will achieve desirable scrotal size by one year of age.

Relationships among seminal culture, seminal white blood cells, and the percentage of primary sperm abnormalities in bulls evaluated prior to the breeding season.

Semen samples from 100 beef breed bulls were evaluated for sperm morphology (phased contrast microscopy), seminal white blood cells, and the presence of potential reproductive pathogens. Eligibility required visualization of the glans penis throughout semen collection. Based on clinical spermiograms, bulls were grouped into normal, marginal, or unsatisfactory morphology classifications. The 3 experimental groups were similar in age and scrotal circumference and differed significantly in the percentage of primary sperm abnormalities. Most semen samples (94%) contained one or more potential reproductive pathogens (Hemophilus somnus. Mycoplasma bovigenitalium, Arcanobacterium pyogenes and Ureaplasma diversum). No significant relationship could be demonstrated between primary abnormalities and the assigned culture score. Our experimental results suggest that clinicians should interpret clinical semen culture results with great care. No significant relationship could be demonstrated between primary abnormalities and assigned white blood cell (WBC) score, although, only 1% of the samples was scored >5 WBC per high power field. The use of seminal WBC score may be valid adjunct to routine semen evaluation when that threshold is the basis for clinical decisions.

Descriptive epidemiology of anestrus in Michigan Holstein-Friesian cattle.

Twenty-two Michigan Holstein-Friesian herds were studied to determine the incidence and epidemiology of anestrus. In 3,309 lactations studied, 42% were classified as having exhibited preservice anestrus (no estrus detected by 70 d after calving). Organic reasons (pyometra, cystic follicles, static ovaries) were identified by palpation per rectum for 237 (23%) of the cows with preservice anestrus that were examined by a veterinarian. Postservice anestrus, defined as failure to show estrus within 35 d after an unsuccessful insemination, was identified in 790 (47%) of 1,691 lactations. Veterinary examination identified 104 (20%) of postservice anestrous cows as having this condition because of organic causes. The average cow with preservice anestrus had an increase of 30 d open compared to her herdmates, and the average cow with postservice anestrus had an increase of 37 d open. Anestrous cows produced more milk than their unaffected herdmates in both the current and the previous lactation. Analysis of composite lactation curves indicates that, for preservice anestrus, this additional milk production was obtained gradually over the entire lactation. Anestrous cows were culled at a significantly higher rate than their herdmates. Cows with preservice anestrus were more likely to have begun their lactation in the spring months.

The use of embryo collection techniques in Holstein heifers: A model to study early embryonic death.

Twenty-three cyclic Holstein heifers were purchased for use as embryo donors to study the effect of intrauterine exposure to Haemophilus somnus on the number, quality, and viability of embryos produced. Few problems were encountered using standard superovulation and nonsurgical embryo collection techniques on virgin heifers. Based on three or more ovulations, as determined by palpation per rectum of the ovaries at the time of embryo recovery, 28 of 30 heifers responded to the superovulation regimen. Of 29 nonsurgical recoveries, 27 produced one or more embryos. One hundred and seventy-six embryos and ova were collected from heifers synchronized, superovulated, and flushed 7 to 8 d after insemination.