Race and sex associations with tacrolimus pharmacokinetics in stable kidney transplant recipients.

STUDY OBJECTIVE: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients. DESIGN AND SETTING: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC0-12 ), AUC0-4 , 12-h troughs (C12 h ), maximum concentrations (Cmax ), oral clearance (Cl), with dose-normalized AUC0-12 , troughs, and Cmax with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7) metabolic composite, and ATP binding cassette gene subfamily B member 1 (ABCB1) polymorphisms. PATIENTS: 65 stable, female and male, Black and White kidney transplant recipients receiving tacrolimus and mycophenolic acid ≥6 months post-transplant were evaluated. MEASUREMENTS AND MAIN RESULTS: Black recipients exhibited higher tacrolimus AUC0-12 (Race: p = 0.005), lower AUC* (Race: p < 0.001; Race × Sex: p = 0.068), and higher Cl (Race: p < 0.001; Sex: p = 0.066). Greater cumulative (Sex: p < 0.001; Race × Sex: p = 0.014), neurologic (Sex: p = 0.021; Race × Sex: p = 0.005), and aesthetic (Sex: p = 0.002) adverse effects were found in females, with highest scores in Black women. In 84.8% of Black and 68.8% of White patients, the target AUC0-12 was achieved (p = 0.027). In 31.3% of White and 9.1% of Black recipients, AUC0-12 was <100 ng‧h/ml despite tacrolimus troughs in the target range (p = 0.027). The novel CYP3A5*3*6*7 metabolic composite was the significant covariate accounting for 15%-19% of tacrolimus variability in dose (p = 0.002); AUC0-12 h * (p < 0.001), and Cl (p < 0.001). CONCLUSIONS: Tacrolimus pharmacokinetics and adverse effects were different among stable kidney transplant recipient groups based upon race and sex with interpatient variability associated with the CYP3A5*3*6*7 metabolic composite. More cumulative, neurologic, and aesthetic adverse effects were noted among females. Tacrolimus regimens that consider race and sex may reduce adverse effects and enhance allograft outcomes by facilitating more patients to achieve the targeted AUC0-12 h .

Association of ABCC2 Haplotypes to Mycophenolic Acid Pharmacokinetics in Stable Kidney Transplant Recipients.

Mycophenolic acid exhibits significant interpatient pharmacokinetic variability attributed to factors including race, sex, concurrent medications, and enterohepatic circulation of the mycophenolic acid glucuronide metabolite to mycophenolic acid. This conversion by enterohepatic circulation is mediated by the multidrug resistance-associated protein 2, encoded by ABCC2. This study investigated ABCC2 haplotype associations with mycophenolic acid pharmacokinetics in 147 stable kidney transplant recipients receiving mycophenolic acid in combination with calcineurin inhibitors. The role of the ABCC2 genotypes -24C>T (rs717620), 1249C>T (rs2273697), and 3972C>T (rs3740066) were evaluated in prospective, cross-sectional pharmacokinetic studies of stable recipients receiving mycophenolic acid and either tacrolimus or cyclosporine. Haplotype phenotypic associations with mycophenolic acid pharmacokinetic parameters were computed using THESIAS (v. 3.1). Four ABCC2 haplotypes with estimated frequencies greater than 10% were identified (H1:CGC [wild type], H9:CGT, H2:CAC, H12:TGT). There were no differences in haplotype frequencies by either race or sex. There were significant associations of pharmacokinetic parameters with ABCC2 haplotypes for mycophenolic acid clearance (L/h), mycophenolic acid AUC0-12h (mg·h/L), and the ratio of mycophenolic acid glucuronide to mycophenolic acid AUC0-12h . The wild-type haplotype ABCC2 CGC had greater mycophenolic acid AUC0-12h (P = .017), slower clearance (P = .013), and lower mycophenolic acid glucuronide to mycophenolic acid AUC0-12h ratio (P = .047) compared with the reduced function ABCC2 haplotype CGT. These differences were most pronounced among patients receiving tacrolimus cotreatment. No phenotypic associations were found with the cyclosporine-mycophenolic acid regimen. Variation in ABCC2 haplotypes contributes to subtherapeutic mycophenolic acid exposure and influences interpatient variability in pharmacokinetic phenotypes based on concurrent calcineurin inhibitor treatment.

Long bonds and short barriers: ionization and isomerization of alkyl nitriles.

Ab initio molecular orbital calculations demonstrate that ionizing alkyl nitriles produces a dramatic geometry change involving lengthening of a C-CH(2)CN bond. The experimental determination of the adiabatic ionization energy of these species is thus very difficult. In addition, there are generally low barriers for 1,2-H shift reactions in the molecular ions leading to RCHCHN(+*) and RCHCNH(+*) isomers, which makes generating pure ionized alkyl nitrile in a mass spectrometer a challenge. Threshold photoelectron spectroscopy and threshold photoelecton photoion coincidence spectroscopy were employed to study the ionization and dissociation of two alkyl nitriles, in particular, pentanenitrile and 2,2-dimethylpropanenitrile. Threshold ionization is shown to result not in the respective molecular ions, but rather in isomeric forms, resulting in dissociation thresholds that lie below the calculated adiabatic ionization energies of the two molecules. Appearance energies for all observed fragment ions are reported and compared to available literature values. Charge separation in the dissociation of doubly ionized 2,2-dimethylpropanenitrile is observed as fragment-ion time-of-flight peak broadening at high photon energies.

Venous thromboembolism prophylaxis: the role of the nurse.

Venous thromboembolism is the most common preventable cause of hospital death, with surgical and medical patients at a significantly increased risk. It is estimated that, without prophylaxis, it occurs in 20% of general medical and surgical patients, and 40-60% of orthopaedic patients. It accounts for 25-times greater mortality than meticillin resistant Staphylococcus aureus (MRSA). Despite overwhelming evidence advocating the routine use of thromboprophylaxis, provision is persistently deficient. It has been demonstrated that involvement of the nursing profession in initiatives to improve provision is important and effective. Recent years have seen the nursing profession continue to evolve and take the lead in a number of areas of preventive medicine, and to develop specialist nursing roles. The authors believe that this drive must be harnessed so that the profession can enact the routine provision of thromboprophylaxis to patients.

Beyond Single Nucleotide Polymorphisms: CYP3A5∗3∗6∗7 Composite and ABCB1 Haplotype Associations to Tacrolimus Pharmacokinetics in Black and White Renal Transplant Recipients.

Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A5 (CYP3A5) isoenzymes and membrane transport by P-glycoprotein. Interpatient pharmacokinetic variability has been associated with genotypic variants for both CYP3A5 or ABCB1. Tacrolimus pharmacokinetics was investigated in 65 stable Black and Caucasian post-renal transplant patients by assessing the effects of multiple alleles in both CYP3A5 and ABCB1. A metabolic composite based upon the CYP3A5 polymorphisms: ∗3(rs776746), ∗6(10264272), and ∗7(41303343), each independently responsible for loss of protein expression was used to classify patients as extensive, intermediate and poor metabolizers. In addition, the role of ABCB1 on tacrolimus pharmacokinetics was assessed using haplotype analysis encompassing the single nucleotide polymorphisms: 1236C > T (rs1128503), 2677G > T/A(rs2032582), and 3435C > T(rs1045642). Finally, a combined analysis using both CYP3A5 and ABCB1 polymorphisms was developed to assess their inter-related influence on tacrolimus pharmacokinetics. Extensive metabolizers identified as homozygous wild type at all three CYP3A5 loci were found in 7 Blacks and required twice the tacrolimus dose (5.6 ± 1.6 mg) compared to Poor metabolizers [2.5 ± 1.1 mg (P < 0.001)]; who were primarily Whites. These extensive metabolizers had 2-fold faster clearance (P < 0.001) with 50% lower AUC∗ (P < 0.001) than Poor metabolizers. No differences in C12 h were found due to therapeutic drug monitoring. The majority of blacks (81%) were classified as either Extensive or Intermediate Metabolizers requiring higher tacrolimus doses to accommodate the more rapid clearance. Blacks who were homozygous for one or more loss of function SNPS were associated with lower tacrolimus doses and slower clearance. These values are comparable to Whites, 82% of who were in the Poor metabolic composite group. The ABCB1 haplotype analysis detected significant associations of the wildtype 1236T-2677T-3435T haplotype to tacrolimus dose (P = 0.03), CL (P = 0.023), CL/LBW (P = 0.022), and AUC∗ (P = 0.078). Finally, analysis combining CYP3A5 and ABCB1 genotypes indicated that the presence of the ABCB1 3435 T allele significantly reduced tacrolimus clearance for all three CPY3A5 metabolic composite groups. Genotypic associations of tacrolimus pharmacokinetics can be improved by using the novel composite CYP3A5∗3∗4∗5 and ABCB1 haplotypes. Consideration of multiple alleles using CYP3A5 metabolic composites and drug transporter ABCB1 haplotypes provides a more comprehensive appraisal of genetic factors contributing to interpatient variability in tacrolimus pharmacokinetics among Whites and Blacks.

Methyl t-butyl ether and methyl trimethylsilyl ether ions dissociate near their ionization thresholds: a TPES, TPEPICO, RRKM, and G3 investigation.

The threshold photoelectron spectra and threshold photoelectron photoion coincidence (TPEPICO) mass spectra of methyl t-butyl ether, (CH(3))(3)COCH(3) (MTBE), and methyl trimethylsilyl ether, (CH(3))(3)SiOCH(3) (MTMSE), have been measured using synchrotron radiation. The effect of silicon substitution on the unimolecular dissociation processes and the threshold photoelectron spectrum has been investigated. Both molecular ions dissociate at low internal energies. For ionized MTBE, the parent ion is no longer observed at an internal energy of only 0.2 eV. For this reason, it was not possible to fit the TPEPICO data to extract reliable thermochemical information. G3 level calculations place the molecular ion 5 kJ mol(-1) above the lowest-energy dissociation products, (CH(3))(2)COCH(3)(+) + (*)CH(3), suggesting the participation of an isomer, potentially the distonic ion (*)CH(2)(CH(3))(2)CO(+)(H)CH(3), in the dissociation. However, the calculations are not considered accurate enough to reliably determine the role this isomer plays, if any. RRKM modeling of the threshold region of the TPEPICO breakdown curves for ionized MTMSE leads to an E(0) for methyl loss of 63 +/- 2 kJ mol(-1), in good agreement with the G3 value of 66 kJ mol(-1). The resulting Delta(f)H(0) for (CH(3))(2)SiOCH(3)(+) of 384 +/- 10 kJ mol(-1) (Delta(f)H(298) = 361 +/- 10 kJ mol(-1)) is 28 kJ mol(-1) lower than the G3 value of 412 kJ mol(-1) due to the G3 Delta(f)H(0) for neutral MTMSE being 16 kJ mol(-1) higher than the previously reported value and the fact that the experimental IE(a) is 6 kJ mol(-1) lower than the G3 estimate. Appearance energy values for higher-energy fragmentation channels up to 36 (for MTBE) and 32 eV (for MTMSE) are reported and compared to literature values. An investigation of fragment ion peak broadening at high internal energy indicated that the two doubly charged molecular ions are not stable on the microsecond time scale. Each was found to dissociate into two singly charged ions along one or more neutral species.

Does tetrahydrofuran ring open upon ionization and dissociation? A TPES and TPEPICO investigation.

The threshold photoelectron spectrum (TPES) of tetrahydrofuran (THF) is compared to that of the unsaturated furan molecule. In general, there is a similarity in the orbital ionization profile for the two species, though unlike furan, THF exhibits (modest) vibrational detail only in the (9b)(-1) X (2)B band. An adiabatic ionization energy of 9.445 +/- 0.010 eV has been derived from the onset of the TPES spectrum. Threshold photoelectron photoion coincidence spectroscopy was used to explore the loss of a hydrogen atom from ionized THF over the photon energy range of 9.9-10.4 eV. RRKM fitting of the resulting breakdown curves yields an E(0) of 0.85 +/- 0.03 eV (82 +/- 3 kJ mol(-1)) (AE = 10.30 +/- 0.04 eV). If the G3 IE of 9.48 eV is used to convert the experimental data from photon energy to THF ion internal energy, E(0) = 0.81 +/- 0.01 eV (78 +/- 1 kJ mol(-1)). The latter value is closer to the G3 E(0) of 72 kJ mol(-1) for the formation of the cyclic ion 1. A variety of ring-opening reactions were also probed at the B3-LYP/6-31+G(d) and G3 levels of theory. The distonic isomer (*)CH(2)CH(2)CH(2)OCH(2)(+) lies 70 kJ mol(-1) higher than ionized THF, which places it within 1 kJ mol(-1) of the threshold for the dissociation to 1. All of the probed H-loss products from the distonic isomer (which includes singlet and triplet species) lie significantly higher in energy than ion 1, eliminating the possibility that ionized THF dissociates to m/z 71 via a ring-opening reaction in the present experiment. The derived Delta(double dagger)S value for the dissociation, 8 +/- 5 J K(-1) mol(-1), is also consistent with the formation of 1. The experimentally derived E(0) values can be used to derive the Delta(f)H(o)(0) for ion 1. Together with the Delta(f)H(o)(0) values for the THF ion (752.0 +/- 2 kJ mol(-1), derived from the neutral Delta(f)H(o)(0) of -154.9 +/- 0.7 kJ mol(-1) and experimental IE of 9.445 +/- 0.010 eV) and H atom (218.5 kJ mol(-1)) our E(0) of 82 +/- 3 kJ mol(-1) yields a Delta(f)H(o)(0) for ion 1 of 620 +/- 4 kJ mol(-1) (Delta(f)H(o)(298) = 594 +/- 4 kJ mol(-1)), in good agreement with the G3 Delta(f)H(o)(0) of 621 kJ mol(-1). Appearance energies for all fragment ions up to photon energies of 34 eV are also reported and discussed in comparison with the available literature.

Influence of Calcineurin Inhibitor and Sex on Mycophenolic Acid Pharmacokinetics and Adverse Effects Post-Renal Transplant.

Tacrolimus or cyclosporine is prescribed with mycophenolic acid posttransplant and contributes to interpatient variability in mycophenolic acid pharmacokinetics and response. Cyclosporine inhibits enterohepatic circulation of the metabolite mycophenolic acid glucuronide, which is not described with tacrolimus. This study investigated mycophenolic acid pharmacokinetics and adverse effects in stable renal transplant recipients and the association with calcineurin inhibitors, sex, and race. Mycophenolic acid and mycophenolic acid glucuronide area under the concentration-time curve from 0 to 12 hours (AUC0-12h ) and apparent clearance were determined at steady state in 80 patients receiving cyclosporine with mycophenolate mofetil and 67 patients receiving tacrolimus with mycophenolate sodium. Gastrointestinal adverse effects and hematologic parameters were evaluated. Statistical models evaluated mycophenolic acid pharmacokinetics and adverse effects. Mycophenolic acid AUC0-12h was 1.70-fold greater with tacrolimus (68.9 ± 30.9 mg·h/L) relative to cyclosporine (40.8 ± 17.6 mg·h/L); P < .001. Target mycophenolic acid AUC0-12h of 30-60 mg·h/L was achieved in 56.3% on cyclosporine compared with 34.3% receiving tacrolimus (P < .001). Mycophenolic acid clearance was 48% slower with tacrolimus (10.6 ± 4.7 L/h) relative to cyclosporine (20.5 ± 10.0 L/h); P < .001. Enterohepatic circulation occurred less frequently with cyclosporine (45%) compared with tacrolimus (78%); P < 0.001; with a 2.9-fold greater mycophenolic acid glucuronide AUC0-12h to mycophenolic acid AUC0-12h ratio (P < .001). Race did not affect mycophenolic acid pharmacokinetics. Gastrointestinal adverse effect scores were 2.2-fold higher with tacrolimus (P < .001) and more prominent in women (P = .017). Lymphopenia was more prevalent with tacrolimus (52.2%) than cyclosporine (22.5%); P < 0.001. Calcineurin inhibitors and sex contributed to interpatient variability in mycophenolic acid pharmacokinetics and adverse effects post-renal transplant, which could be attributed to differences in enterohepatic circulation.

Primary pull-through for Hirschsprung's disease: comparison of open and laparoscopic-assisted procedures.

Rectosigmoid Hirschsprung's disease is usually amenable to minimally invasive primary neonatal pull-through. This may be performed either entirely transanally or with laparoscopic assistance for biopsies with or without colonic mobilization. In our center, all dissection is performed transanally; laparoscopy is used for obtaining colonic biopsies and orientation of the pulled-through bowel segment. In this paper, we describe our initial experience of a consecutive cohort of 20 one-stage laparoscopic-assisted endorectal pull-through (LAEPT) procedures. A historic consecutive cohort of 22 infants who underwent the same open endorectal pull-through (OPT) with open transabdominal mobilization was used for comparison. Age at operation and mean theater time were not significantly different. The mean postoperative stay was significantly reduced in the laparoscopic group (LAEPT 3.8 days vs. OPT 9.5 days; P = 0.0002). Readmission and enterocolitis rates in the first postoperative year did not differ significantly. LAEPT permits early intraoperative biopsies with a visualization of the pull-through to prevent twisting of the bowel.

Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression With Sex and ABCB1 Haplotypes.

Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant complications. AEs may result from intracellular CNI accumulation and low activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 patients receiving tacrolimus and enteric coated mycophenolate sodium or cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment determined individual and composite gastrointestinal, neurologic, aesthetic, and cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined with haplotype associations computed using the THESIAS program, and evaluated by immunosuppression, sex and race using multivariate general linear models. Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores compared with cyclosporine with association to CTT (P = 0.018) and sex (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes and sex were associated with extrarenal AEs. Using haplotypes, certain female patients manifested more AEs regardless of CNI. Haplotype testing may identify patients with greater susceptibility to AEs and facilitate CNI individualization.

Influence of sex and race on mycophenolic acid pharmacokinetics in stable African American and Caucasian renal transplant recipients.

BACKGROUND AND OBJECTIVES: No evaluation of sex and race influences on mycophenolic acid (MPA) pharmacokinetics and adverse effects (AEs) during enteric-coated mycophenolate sodium (ECMPS) and tacrolimus immunosuppression are available. The primary objective of this study was to investigate the influence of sex and race on MPA and MPA glucuronide (MPAG) pharmacokinetics in stable renal transplant recipients receiving ECMPS and tacrolimus METHODS: The pharmacokinetics of MPA and MPAG and their associated gastrointestinal AEs were investigated in 67 stable renal transplant recipients: 22 African American males (AAMs), 13 African American females (AAFs), 16 Caucasian males (CMs), and 16 Caucasian females (CFs) receiving ECMPS and tacrolimus. A validated gastrointestinal AE rating included diarrhea, dyspepsia, vomiting, and acid-suppressive therapy was completed. Apparent clearance, clearance normalized to body mass index (BMI), area under the concentration-time curve from time zero to 12 h (AUC12) and dose-normalized AUC12 (AUC*) were determined using a statistical model that incorporated gastrointestinal AE and clinical covariates. RESULTS: Males had more rapid apparent MPA clearance (CMs 13.8 ± 6.27 L/h vs. AAMs 10.2 ± 3.73 L/h) than females (CFs 8.70 ± 3.33 L/h and AAFs 9.71 ± 3.94 L/h; p = 0.014) with a race-sex interaction (p = 0.043). Sex differences were observed in MPA clearance/BMI (p = 0.033) and AUC* (p = 0.033). MPA AUC12 was greater than 60 mg·h/L in 57 % of renal transplant recipients (RTR) with 71 % of patients demonstrating gastrointestinal AEs and a higher score noted in females. In all patients, females exhibited 1.40-fold increased gastrointestinal AE scores compared with males (p = 0.024). Race (p = 0.044) and sex (p = 0.005) differences were evident with greater MPAG AUC12 in AAFs and CFs. CONCLUSION: Sex and race differences were evident, with females having slower MPA clearance, higher MPAG AUC12, and more severe gastrointestinal AEs. These findings suggest sex and race should be considered during MPA immunosuppression.

Early adult outcome of the Duhamel procedure for left-sided Hirschsprung disease--a prospective serial assessment study.

PURPOSE: To assess both early adult functional outcome and change in long-term functional outcome over time after the Duhamel procedure (DP) for left-sided Hirschsprung disease (HSCR). METHODS: The study population consisted of 78 children (aged 19.9 +/- 3.6 years) who previously underwent objective outcome assessment after DP was performed for HSCR during the period of 1980 to 1991. Inclusion criteria were previous evaluation of functional outcome and either rectosigmoid or left-sided HSCR. Outcome measures were assessed twice within the cohort, in 1997 and in 2005. The primary outcome measure was the Rintala (J Ped Surg. 1995;30:491-494) functional outcome score (FOS; maximum, 20). Controls consisted of 20 age-matched healthy children. Satisfactory functional score was defined as an FOS at or above the 10th percentile of controls (FOS, > or = 17). Secondary outcome measures were the operation failure rate (defined by requirement for a stoma or major reoperative surgery), and enterocolitis rates (defined by intention to treat). Consecutive outcome scores were compared by paired t test. Data were expressed as mean +/- SD, and P < .05 was considered significant. RESULTS: Operation failure occurred in 9 (11.5%) of 78. Consecutive FOSs were obtained in 40 (57%) of 69. A satisfactory functional score was observed in 23 (58%) of 40 adults as opposed to 33 (47%) of 70 children 8 years previously (P = .02). Satisfactory outcome (defined by satisfactory functional score and lack of enterostomy or major revision pull-through procedure) was observed in 23 (47%) of 49. Previously, this figure was 34 (44%) of 78. Individual paired FOSs showed a significant improvement with time (1997: 14.9 +/- 4.1; 2005: 16.4 +/- 2.8; P = .02). CONCLUSIONS: At early adult follow-up, the operation failure rate has not changed from that of the same cohort 8 years earlier. However, a significant improvement in individual FOSs was demonstrated.

A photoelectron and TPEPICO investigation of the acetone radical cation.

The valence shell photoelectron spectrum, threshold photoelectron spectrum, and threshold photoelectron photoion coincidence (TPEPICO) mass spectra of acetone have been measured using synchrotron radiation. New vibrational progressions have been observed and assigned in the X 2B2 state photoelectron bands of acetone-h6 and acetone-d6, and the influence of resonant autoionization on the threshold electron yield has been investigated. The dissociation thresholds for fragment ions up to 31 eV have been measured and compared to previous values. In addition, kinetic modeling of the threshold region for CH3* and CH4 loss leads to new values of 78 +/- 2 kJ mol(-1) and 75 +/- 2 kJ mol(-1), respectively, for the 0 K activation energies for these two processes. The result for the methyl loss channel is in reasonable agreement with, but slightly lower than, that of 83 +/- 1 kJ mol(-1) derived in a recent TPEPICO study by Fogleman et al. The modeling accounts for both low-energy dissociation channels at two different ion residence times in the mass spectrometer. Moreover, the effects of the ro-vibrational population distribution, the electron transmission efficiency, and the monochromator band-pass are included. The present activation energies yield a Delta(f)H298 for CH3CO+ of 655 +/- 3 kJ mol(-1), which is 4 kJ mol(-1) lower than that reported by Fogleman et al. The present Delta(f)H298 for CH3CO+ can be combined with the Delta(f)H298 for CH2CO (-47.5 +/- 1.6 kJ mol(-1)) and H+ (1530 kJ mol(-1)) to yield a 298 K proton affinity for ketene of 828 +/- 4 kJ mol(-1), in good agreement with the value (825 kJ mol(-1)) calculated at the G2 level of theory. The measured activation energy for CH4 loss leads to a Delta(f)H298 (CH2CO+*) of 873 +/- 3 kJ mol(-1).