Growth and differentiation of normal and leukemic human bone marrow cells cultured in diffusion chambers.

Bone marrow from healthy, normal volunteers and patients with acute myelocytic leukemia was cultured in diffusion chambers implanted into cyclophosphamide pretreated mice. Chambers were removed at regularly scheduled intervals over a period of 28 days. Total and differential cell counts were then done on the contents of each chamber. Normal human bone marrow showed an orderly pattern of growth and differentiation which was not found with leukemic bone marrow. Monocytes and macrophages were the predominant cell types in the diffusion chambers filled with normal marrow after day 10 of culture. Although leukemic specimens showed predominantly leukemic cells, a few mature polymorphonuclear leukocytes could be found throughout the entire culture period. Questions about the nature of the defect in acute myelocytic leukemia and the significance of the in vivo culture system are discussed. The results of these studies are compared and contrasted with studies of a similar type.

Hydroxamic acid-based bisubstrate analog inhibitors of Ras farnesyl protein transferase.

The rational design, synthesis, and activity of novel, hydroxamic acid-based, collective bisubstrate analog inhibitors of farnesyl protein transferase (FPT) is described. This class of compounds differ structurally from the conventional FPT inhibitors by being non-sulfhydryl and by being bisubstrate based rather than peptide or FPP derived inhibitors. Whereas replacement of the sulfhydryl group of tetrapeptide CVLS (I50 = 1 microM) by an N-methylhydroxamic acid had a deleterious effect (10, I50 > 360 microM), moderate inhibition was realized with 16 (I50 = 42.5 microM), a bisubstrate analog involving anchorage of farnesyl and tripeptide groups by a hydroxamic acid-embedded linker. Starting from 16, a 1 order of magnitude improvement in in vitro potency was obtained by optimization of the linker (20, I50 = 4.35 microM). An additional 13-fold enhancement was achieved by substituting the tripeptide moiety VLS in 20 by VVM (23, I50 = 0.33 microM). The dependence of these inhibitors on their peptide and farnesyl subunits is suggestive of their bisubstrate nature. Compound 23 (I50 = 0.33 microM) is 2 orders of magnitude better in activity compared to the initial lead 16 [I50 = 42.5 microM) and is effective in blocking prenylation of protein in whole cells including p21ras.

Phosphinyl acid-based bisubstrate analog inhibitors of Ras farnesyl protein transferase.

The rational design, synthesis, and biological activity of phosphonyl- and phosphinyl-linked bisubstrate analog inhibitors of the enzyme Ras farnesyl protein transferase (FPT) are described. The design strategy for these bisubstrate inhibitors involved connection of the critical binding components of the two substrates of FPT (ras protein and farnesyl pyrophosphate, FPP) through a phosphonyl- or phosphinyl-bearing linker. Compound 14, the first example in this series, was found to be a potent FPT inhibitor (I50 = 60 nM). A further 15-fold enhancement in activity was observed upon replacement of the VLS tripeptide sequence in 14 with VVM (15, I50 = 6 nM). The phosphinic acid analog 16 (I50 = 6 nM) was equiactive to phosphonic acid 15. Compounds 14-16 afforded 1000-fold selectivity for FPT against the closely related enzyme geranylgeranyl protein transferase type I, GGT-I [14, I50(GGT-I) = 59 microM; 15 I50(GGT-I) = 10 microM; 16 I50(GGT-I) = 21 microM]. Methyl and POM ester prodrugs 17-19 were prepared and evaluated in whole cell assays and appear to block ras-induced cell transformation, as well as colony formation in soft agar. A distinctive feature of this novel class of potent and selective bisubstrate FPT inhibitors is that they are non-sulfhydryl in nature.

Synthesis and antiviral activity of 1-cyclobutyl-5-(2-bromovinyl)uracil nucleoside analogues and related compounds.

A series of racemic (1 alpha (E), 2 beta, 3 alpha)-1-[2,3-bis(hydroxymethyl)cyclobutyl]-5-(2-halovinyl)uracils was synthesized and evaluated in cell culture. The bromovinyl, iodovinyl, and chlorovinyl analogues, 13, 15, and 16, respectively, are all potent inhibitors of varicella zoster virus (VZV), but are less inhibitory to the replication of human cytomegalovirus (HCMV) and herpes simplex viruses 1 and 2 (HSV-1, HSV-2). The excellent anti-VZV activities of 13, 15, and 16 coupled with their virtual inability to inhibit WI-38 cell growth indicate high in vitro therapeutic indices. VZV thymidine kinase readily converts these compounds to their respective monophosphates but not to their corresponding diphosphates. Compound 13a, the (1'R) enantiomer of the bromovinyl analogue 13, was also synthesized, and its potency is comparable to that of the racemate. A lower homologue 14, (1 alpha (E),2 beta, 3 alpha)-1-[2-hydroxy-3-(hydroxymethyl)cyclobutyl]-5- (2-bromovinyl)uracil, was found to be inactive against VZV, HCMV, HSV-1, and HSV-2.

Broad-spectrum antiviral activity of the acyclic guanosine phosphonate (R,S)-HPMPG.

(R,S)-9-(3-hydroxy-2-phosphonomethoxypropyl)guanine [(R,S)-HPMPG] exhibits broad spectrum antiviral activity with an ED50 of less than 1 microM against herpes simplex virus (HSV) types 1 and 2, varicella zoster virus, human cytomegalovirus (HCMV) and vaccinia in plaque reduction assays. Wild type HSV-2 and its thymidine kinase deficient variant are equally sensitive to (R,S)-HPMPG. (R,S)-HPMPG is 100-fold more potent than acyclovir (ED50 = 0.45 microM vs. 44 microM, respectively) against HCMV in cell culture, and 10-fold more active than acyclovir in extending survival time in mice intraperitoneally infected with 70 LD50 HSV-1. However, (R,S)-HPMPG is toxic when administered repeatedly at 44 mg/kg/day in uninfected adult mice. The diphosphoryl derivative of HPMPG was enzymatically synthesized and is a competitive inhibitor of HSV-1 DNA polymerase relative to dGTP (K1 = 0.03 microM). HPMPG-PP is 70-fold less active at inhibiting HeLa DNA polymerase alpha than HSV-1 DNA polymerase. At concentrations between 0.3 and 1.5 microM (R,S)-HPMPG inhibited HSV-1 DNA replication greater than or equal to 50% in infected cells as measured by nucleic acid hybridization. Consistent with inhibition of viral DNA synthesis, 6 to 30 microM (R,S)-HPMPG reduces late viral polypeptide synthesis in HSV-1 infected cells. These data indicate that (R,S)-HPMPG is a thymidine kinase independent broad spectrum antiviral drug which is capable of inhibiting viral DNA polymerase.

Gender-, side- and site-dependent variations in human perioral spatial resolution.

Twenty-eight right-handed, young adults participated in a sensory testing experiment to evaluate spatial resolution at 10 positionally matched sites on the right- and left-hand sides of the face. An adaptive psychophysical (i.e. tracking) procedure was used to estimate the threshold spatial separation for perceiving two points of contact at each site. Estimates of the threshold at one site on both sides of the face were also obtained with a method-of-limits procedure similar to that employed for clinical evaluation of patients. In addition, each individual was asked to rate (i) his(her) overall facial sensitivity to touch and (ii) the degree to which he(she) could discern subtle changes in lip, cheek and chin position during speech, chewing and facial expression. Analysis of the estimates of the threshold separation obtained with the tracking procedure revealed a significant effect of gender (p < 0.04) and of site (p < 0.001). Females were more spatially sensitive than males: average threshold separations were 1.55 mm less. Most notably, the threshold increased ninefold with distance posterolaterally from the oral opening. The vermilion of the upper lip was the most spatially sensitive site (population geometric mean = 2.4 mm) and the preauricular skin the least spatially sensitive site (20.9 mm). Significant effects of side and of interactions among gender, side and site were not observed. The estimates obtained with the method-of-limits procedure were very similar to those obtained with the tracking procedure: the latter were 0.67 mm less on the average. Individuals' ratings of overall facial sensitivity to touch were similar for males and females (p > 0.70). Females, however, reported greater ability to discern subtle changes in lip, cheek and chin position than males (p < 0.03). The ratings of this sensory function correlated negatively with the estimates of the threshold separation on the vermilion of the upper lip (p < 0.03).

Bacterial production of 7-formamidocephalosporins. Isolation and structure determination.

Two new 7-formamidocephalosporins have been isolated as their acetyl derivatives (SQ 28,516 and SQ 28,517) from fermentations of a Flavobacterium sp. SC 12,154. Structure 1 was deduced for SQ 28,516 from its spectroscopic properties while structure 2 was proposed for SQ 28,517. SQ 28,516 exhibits weak antibacterial activity.

Diastereomeric 7-ureidoacetyl cephalosporins. I. Superiority of 7alpha-H-L-isomers over D-isomers.

The synthesis and in vitro structure-activity relationship of 7-ureidoacetyl cephalosporins carrying various substituents in the 3-position, compounds that showed an enhanced broad spectrum of antibacterial activity, has been outlined. Contrary to most of the previous observations with diastereomeric isomers of cephalosporins, it has been found that the L-side chain isomers also are very potent antibiotics and are even more active inhibitors of certain beta-lactamase-producing Gram-negative bacteria than the corresponding D-side chain isomers. SQ 69,613, 7beta-[[L-[(aminocarbonyl)amino]-2-furanylacetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl) thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, sodium salt, the most active compound tested, except for activity against staphylococci, was as active in vitro as cefamandole.

Diastereomeric 7-ureidoacetyl cephalosporins. II. 7beta [[[(Aminocarbonyl) amino]-2-thienylacetyl] amino]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl) thio] methyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.

The synthesis and antibacterial activity in vitro of 7-methoxylated cephalosporins having a thienylureidoacetyl or a thienylglycyl C-7 side-chain are described. Acylation of 7 beta-amino-7-methoxycephems with a novel 2-aminooxazolone hydrochloride under neutral conditions gave the thienylureidoacetyl derivatives in good yield with retention of configuration. 7 beta-[[D-[(Aminocarbonyl)amino]-2-thienylacetyl]amino]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio] methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt (SQ 14,359) was found to have a broad-spectrum of antibacterial activity in vitro, particularly against beta-lactamase-producing organisms.

End-of-life issues: a survey of English-speaking Canadian nurses in AIDS care.

This anonymous postal survey explored attitudes and experiences concerning end-of-life decisions. Respondents were English-speaking members of the Canadian Association for Nurses in AIDS Care (CANAC) and other nurses identified as working primarily in HIV/AIDS settings. Seventy-three percent believed that the law should be changed to allow physicians to practice voluntary euthanasia (VE) and assisted suicide (AS). Fifty-three percent indicated that nurses should be allowed to practice VE and AS. Although VE and AS are illegal, fewer than one in five nurses would report a colleague whom they knew to be involved in such acts. More than one in five nurses have received requests from patients to hasten their deaths by VE. Nearly 98% believe that the nursing profession should be involved in policy development concerning VE and AS, and nearly 78% believe that nurses should be involved in the decision-making process with patients if such acts were legal. Given that ethical codes for Canadian nurses promote client self-determination and that nurses are the largest group of care providers for the terminally ill, the profession must promote discussion and research if it is to take a leadership role with respect to end-of-life issues.

Comparison of three methods of feeding sows in gestation and the subsequent effects on lactation performance.

A total of 684 sows from breeding groups over 6 wk was used to compare three methods of feeding during gestation on gestation and lactation performance. Control gilts and sows were fed according to body condition based on a scale of 1 to 5 (1 = thin, 5 = fat). Sows were visually assessed for body condition at breeding and were assigned a daily feed allowance to achieve a BCS of 3 at farrowing. Treatment 2 used feeding levels based on backfat thickness (measured between d 0 and 5 after breeding) and weight at weaning for sows or service for gilts. Feed allowance was calculated to achieve a target backfat of 19 mm at farrowing, and remained constant from d 0 to 101 of gestation. Feed allowances were based on modeled calculations of energy and nutrient requirements to achieve target sow maternal weight and backfat gains. Treatment 3 was identical to Treatment 2, except that feeding pattern was altered for thin sows and gilts (<15 mm at service) in an attempt to reach 19 mm by d 36 of gestation. Sows were weighed at the previous weaning, and gilts were weighed at service, with both weighed again between d 112 and 114 of gestation. Backfat was measured between d 0 and 5, and again between d 108 and 113 of gestation. At farrowing, sows on Treatments 2 and 3 had 19 and 19.1 mm of backfat, respectively, whereas control sows tended to have greater (P < 0.07) backfat (20 mm). On average, sows targeted to gain 6 to 9 mm of backfat failed to reach target gains regardless of feeding method. Feeding sows in gestation based on backfat (Treatments 2 and 3) resulted in a numerically higher proportion of sows in the target backfat range of 17 to 21 mm (40.2, 53.3, and 52.6% for control and Treatments 2 and 3, respectively) at farrowing and a numerically lower percentage of fat sows (>21 mm), but no difference in the percentage of thin sows (<17 mm) compared with feeding based on body condition. In conjunction with this observation, sows fed based on BCS were fed higher (P < 0.05) feeding levels in gestation than were sows fed based on backfat depth. Gestation feeding method had no effect on performance during lactation. Feed intake in lactation was lower (P < 0.05) for high backfat sows (>21 mm) at farrowing compared with sows with <21 mm. The high proportion of sows in the optimal backfat category demonstrates that feeding based on backfat and BW has potential for facilitating more precise feeding during gestation.

Influence of Carnichrome on the energy balance of gestating sows.

Twelve multiparous sows with an average initial weight of 182 kg were used in a randomized complete block design to determine the effects of feeding Carnichrome (50 mg of carnitine and 200 microg of chromium picolinate per kilogram of feed, as fed) on energy and nitrogen utilization in early, mid-, and late gestation. All sows were fed a diet with or without Carnichrome for the preceding 28-d lactation, the weaning-to-estrus period, and for the duration of gestation. Daily feeding allowances over pregnancy were based on calculated energy and nutrient requirements to achieve a target sow maternal weight gain of 20 kg and remained constant throughout gestation. Heat production (HP) and its partitioning (activity, thermic effect of feeding short term [TEFst], basal) were determined in early (wk 5 or 6), mid- (wk 9 or 10), and late (wk 14 or 15) pregnancy using indirect calorimetry. Net maternal weight gain and total number of fetuses averaged 21.6 kg and 16.4, respectively. Organic matter and energy digestibility for the Carnichrome diet was greater (P < 0.05), which resulted in greater DE and ME contents (0.6%, P < 0.05) compared with the control diet. The digestibility coefficient of energy in the current experiment for a typical corn and soybean meal diet (92%) was greater than that predicted from DE values of corn and soybean meal in feeding tables (88%). Carnichrome had no effect on total HP, energy retained as protein or lipid, and maternal energy retention in early, mid-, or late gestation. Heat production in late gestation increased linearly (4.0 kJ/[kg BW0.75 x d]) for each additional day from d 90 to 110, despite the reduction of ME intake per unit of BW0.75. Metabolizable energy requirement for maintenance was 405 kJ/(kg BW0.75 x d). On average, activity HP was 116 kJ/(kg BW0.75 x d), which was equivalent to 20% of ME intake; however, this value ranged from 11 to 37% between sows, which corresponds to duration of standing ranging from 210 to 490 min/d. Energy cost of standing activity averaged 0.30 kJ/(kg BW0.75 x min). In conclusion, Carnichrome had no effect on the components of heat production and maternal weight gain during gestation, although it improved energy and organic matter digestibility of the diet.

Medicine and the law: treatment of minors--consent requirements.

PIP: The Texas Family Code specifies the persons who may consent to a minor's medical treatment when the person having the power to consent cannot be contacted and when that absent person has not indicated a refusal to consent. It also specifies the content and circumstances under which consent must be given. Texas law provides for an exception to the general principle that minors are legally incapable of giving consent to treatment and the basis for this exception is specified. Physicians, dentists, hospitals, or other medical facilities may rely on the minor's written statement of the basis for his/her independent consent under Section 35.03, and physicians who examine and treat minors under this section are liable only for their own acts of negligence. When a minor consents to care under Section 35.03, parallel consent by parents, a managing conservator, or guardian (persons in loco parentis) is not legally required, but an individual physician may decide to impose whatever conditions regarding consent he or she sees fit before agreeing to treat a minor. In 1973 the US Supreme Court declared unconstitutional all Texas abortion statues which were placed before it for review in the case of Roe vs. Wade. The 1974 opinion of the Texas Attorney General that "there are now no laws in the state regulating abortion per se," remains substantially correct. Supreme Court findings in cases concerning minors and abortions indicate that a physician in Texas, who performs an abortion at the request of an emancipated minor who is sufficiently mature and well informed to make the decision, will not be held liable in civil damages to the minor's parents for operating without their consent. In Carey vs. Population Services International, the Supreme Court struck down a New York statute which made criminal the sale or distribution of contraceptives of any kind to minors under age 16, insofar as it applied to nonprescription contraceptives. The US Court of Appeals for the 6th Circuit held in Doe vs. Irwin that a publicly operated family planning clinic in Michigan did not unconstitutionally infringe on parents' rights by distributing contraceptive devices and medication to unemancipated minors without parental consent or prior notification. No state statute requiring notification or consent was involved, and the court's opinion did not discuss this issue. Section 35.03(3) of the Texas Family Code enables minors to consent to the diagnosis and treatment of any infectious, contagious, or communicable disease. Thus a minor could consent independently to treatment for the 3 named venereal diseases, but presumably not for treatment of a sexually transmitted disease such as herpes.^ieng

Reporting peer review actions to the Texas State Board of Medical Examiners.

This article originally was prepared for presentation at the 1988 Texas Health Law Conference, Nov 4, 1988, in Austin. It appears this month in Texas Medicine to emphasize the importance of state and federal laws that require reporting of certain peer review actions by hospitals, medical societies, and other organizations to the Texas State Board of Medical Examiners (TSBME). The author, Michael G. Young, is staff counsel for the TSBME. He formerly was staff attorney and director, Office of Medical Ethics, at Texas Medical Association.

Nutritional value of full-fat green canola seed fed to growing-finishing pigs.

Immature green canola seed (full-fat green canola seed [FFGC]) is rejected by canola crushing plants due to chlorophyll staining of oil destined for human consumption. With >35% oil, FFGC can contribute energy to pig diets. The nutritive value of FFGC for growing-finishing pigs was determined in 2 studies. In Exp. 1, 6 ileal-cannulated barrows (46.5 kg BW) were fed 3 diets as a replicated 3 × 3 Latin square to determine standardized ileal digestible (SID) coefficients of AA and calculate DE and NE values for FFGC. A diet including 40% FFGC replaced wheat in a basal diet and a cornstarch-based N-free diet were fed to determine energy and nutrient digestibility by difference and to estimate basal endogenous AA losses to calculate SID of AA. In Exp. 2, 1,100 pigs (32.9 kg BW), housed in 50 pens of 22 barrows or gilts per pen, were fed 5 diets including 0, 5, 10, and 15% constant or declining amounts (15, 10, 5, 0, and 0%, respectively) of FFGC over 5 phases to determine effects of feeding FFGC on growth performance and carcass characteristics. Phase diets were formulated to provide 4.00, 3.60, 3.25, 2.90, and 2.65 g SID Lys/Mcal NE for d 0 to 21, d 22 to 42, d 43 to 62, d 63 to 74, and d 75 to 123 kg market weight. Carcass characteristics were measured using the Destron grading system. On DM basis, FFGC contained 43% ether extract, 25% CP, 22% NDF, 10 µmol/g glucosinolates, 1.35% Lys, 0.5% Met, 0.9% Thr, and 0.27% Trp. In FFGC, SID coefficients of Lys, Met, Thr, and Trp were 86.9, 87.3, 76.9, and 84.3%, respectively, and calculated DE and NE values were 4.92 and 3.50 Mcal/kg of DM, respectively. Overall, increasing dietary FFGC inclusion from 0 to 15% linearly decreased (P < 0.05) G:F, carcass weight, and dressing percentage (0.392 to 0.381 kg/kg, 96.7 to 95.7 kg, and 78.4 to 77.8%, respectively) and tended to decrease (P = 0.078) ADG. Pigs fed decreasing amounts of FFGC by growth phase compared with controls (0% FFGC) had lower (P = 0.011) overall G:F (0.392 vs. 0.372 kg/kg). Increasing dietary FFGC inclusion did not affect carcass backfat thickness and loin depth. The FFGC was a good source of dietary energy and AA. However, increasing dietary FFGC inclusion for pigs reduced G:F and dressing percentage likely because of the increased dietary fiber content, resulting from increasing FFGC and barley and reducing wheat, soybean meal, and tallow in diets. Inclusion of FFGC in swine diets should, therefore, be based on targeted G:F and relative cost to other feedstuffs.

Effects of increasing co-product inclusion and reducing dietary protein on growth performance, carcass characteristics, and jowl fatty acid profile of growing-finishing pigs.

Dietary inclusion of co-products (Co-P) provides opportunities for diversifying the feedstuff matrix by using local feedstuffs, reducing feed costs, and producing value-added pork. In 2 studies, we determined effects of Co-P (canola meal, distillers dried grains with solubles, and co-extruded oil seed and field pea) inclusion level and reduced dietary CP concentration on growth performance, carcass characteristics, and jowl fatty acid profiles of growing-finishing pigs. Pigs were fed isoenergetic and isolysinic diets over 4 growth phases with 8 pen observations per dietary regimen. At slaughter, carcasses were characterized for all pigs and jowl fat was collected from 2 pigs per pen. In Exp. 1, 1,056 pigs (initial BW, 35.3 ± 0.4 kg) were fed 3 levels of dietary Co-P (low, mid, and high) and 2 CP concentrations (low and normal). Overall (d 0 to 86), increasing Co-P inclusion from low to mid or high decreased (P < 0.001) ADFI and ADG of pigs. Low CP concentration increased (P < 0.05) ADFI and ADG compared with normal CP concentration. An interaction (P = 0.026) occurred between dietary Co-P inclusion and CP concentration for G:F; low CP reduced (P < 0.05) G:F compared with normal CP for pig fed low Co-P, but G:F did not differ between CP concentrations for pigs fed mid and high Co-P. Increasing dietary Co-P inclusion from low to high increased (P < 0.001) α-linolenic acid (ALA) in jowl fat but decreased (P < 0.001) carcass weight and loin depth. In Exp. 2, 1,008 pigs (initial BW, 30.3 ± 0.4 kg) were assigned to 5 dietary regimens with Co-P increasing from 2.0 to 50.0% or a sixth regimen with 10% extra supplemental AA for the 37.5% Co-P diet. Overall (d 0 to 97), increasing Co-P inclusion did not affect ADFI, ADG, and G:F. Increasing dietary Co-P inclusion linearly decreased (P < 0.01) carcass weight, dressing percentage, backfat thickness, and loin depth but linearly increased (P < 0.001) jowl ALA. Supplementing 10% extra AA to the 37.5% Co-P diet did not affect growth performance or dressing percentage but increased (P = 0.014) carcass leanness and decreased (P = 0.023) backfat thickness compared with the 37.5% Co-P diet, indicating that dietary AA supply did not limit BW gain. In conclusion, Co-P can be included by up to 50% in diets for growing-finishing pigs without affecting G:F. However, increasing dietary Co-P may reduce ADG, ADFI, and carcass weight even if diets are balanced for dietary NE and standardized ileal digestible AA content.

The nutritional value of expeller-pressed canola meal for grower-finisher pigs.

Expeller-pressed (EP) canola meal contains more residual oil than solvent-extracted canola meal and might be an attractive feedstuff for swine, but it has been poorly characterized. In Exp. 1, six ileal-cannulated barrows (36 kg of BW) were fed at 3x maintenance either a 44% EP canola meal diet or a N-free diet in a crossover design to measure energy and AA digestibility and calculate standardized ileal digestible (SID) AA and NE content, with 6 observations per diet. Each period consisted of a 5-d diet adaptation and a 2-d feces and 3-d digesta collection. The EP canola meal contained (% of DM) 38.5% CP, 13.3% ether extract, 2.42% Lys, 1.54% Thr, 0.62% Met, and 23.2 micromol/g of glucosinolates. Apparent total tract energy digestibility was 75.0% and the DE and predicted NE content were 3.77 and 2.55 Mcal/kg (in DM), respectively. The SID AA content (% of DM) was 1.77% Lys, 1.04% Thr, and 0.52% Met. In Exp. 2, a total of 1,100 pigs (25 kg of BW) housed in 50 pens were fed 5 dietary regimens with 0, 7.5, 15, and 22.5% or decreasing amounts (22.5, 15, 7.5, and 0%, respectively) of EP canola meal over 4 phases to validate performance and carcass characteristics. Diets were formulated to contain equal NE:SID Lys for each growth phase (g/Mcal; 4.04, d 0 to 25; 3.63, d 26 to 50; 3.23, d 51 to 77; 2.83, d 78 to 90). At slaughter, carcass characteristics were measured for all pigs, and jowl fat was sampled for 2 pigs per pen. For d 51 to 90, the 22.5% EP canola meal regimen was reduced to 18% (22.5/18%) because of decreased ADFI in phases 1 and 2. Overall (d 0 to 90), increasing dietary EP canola meal linearly decreased (P < 0.001) ADG and ADFI and linearly increased (P < 0.01) G:F. For 0 and 22.5/18% EP canola meal, respectively, ADG was 978 and 931 g/d, ADFI was 2.77 and 2.58 kg/d, and G:F was 0.366 and 0.378. Increasing dietary EP canola meal did not alter the carcass backfat thickness, loin depth, or jowl fat fatty acid profile. Pigs fed 22.5/18% EP canola meal reached slaughter weight 3 d after (P < 0.05) pigs fed 0% EP canola meal. In summary, EP canola meal provided adequate energy and AA; however, ADG was reduced by 3 g/d per 1% of EP canola meal inclusion, likely because of increased dietary glucosinolates. Thus, the amount of EP canola meal included in swine diets should be targeted to an expected growth performance and carcass quality. Finally, diets formulated to contain an equal NE and SID AA content did not entirely eliminate the risks for reduced growth performance associated with inclusion of an alternative feedstuff.