Effects of supplemental methionine sources in finishing pig diets on growth performance, carcass characteristics, cutting yields, and meat quality.

Supplemental methionine (Met) is widely used within the swine industry; however, data are limited regarding the effect of Met sources on carcass cutability and meat quality. The objective was to determine the effects of L-Met (LM, 99%), DL-Met (DLM, 99%), or calcium salt of DL-Met hydroxyl analog (MHA, 84%) in finishing pig diets on carcass characteristics and meat quality. At 9 weeks of age, pigs (N = 240) were allocated to 60 single-sex pens for a four-phase finishing trial that lasted 104 d. Pigs were fed a common grower diet until day 56 where pens were randomly allotted to one of the three experimental diets. For the remaining 7 wk of the finisher phase, pigs (BW = 79.9 ±â€…0.80 kg) were fed diets containing LM, DLM, or MHA, with the supplemental Met source providing 25% of standardized ileal digestible (SID) Met + cysteine (Cys) requirement based on 65% bioefficacy for MHA in comparison with LM or DLM. One pig per pen was slaughtered at the study conclusion (on day 104), and the left sides of carcasses were fabricated into subprimal cuts to determine carcass-cutting yields. Loin quality including proximate composition and shear force were measured. Hot carcass weight was not different (P = 0.34) between treatments (LM 104.5 kg; DLM 103.0 kg; MHA 101.5 kg), moreover, loin eye area was not different (P = 0.98) between treatments (LM 52.65 cm²; DLM 52.49 cm²; MHA 52.81 cm²). Boneless carcass-cutting yield was not different (P = 0.56) between treatments (LM 54.97 kg; DLM 54.82 kg; MHA 54.52 kg). Loin pH was not different (P = 0.24) between treatments (LM 5.45; DLM 5.48; MHA 5.45). However, drip loss tended to be reduced (P = 0.11) by the DLM treatment (5.58%) compared with LM (7.03%) and MHA (6.68%) treatments. Shear force was not different (P = 0.85) between treatments (LM 3.03 kg; DLM 3.06 kg; MHA 3.10 kg). However, cook loss tended to be reduced (P = 0.06) by the DLM treatment (16.20%) compared with LM (18.18%) and MHA (18.50%) treatments. These data suggest that only minimal differences in carcass cutability and meat quality can be attributed to Met source in finishing pig diets when using 65% bioefficacy for MHA relative to L-Met or DL-Met.

Cooled feline intestine and fresh intestine did not differ in enterotomy leak pressure testing or in gross wall thickness measurement.

OBJECTIVE: To report gross anatomical gastrointestinal measurements and compare enterotomy leak pressures between fresh and cooled feline cadavers. STUDY DESIGN: Ex vivo, randomized study. ANIMALS: Fresh feline cadavers (n = 20). METHODS: Jejunal segments (8 cm) were harvested on the same day as euthanasia. From each cadaver, one segment was randomly assigned to control (C), fresh enterotomy (FE), and cooled enterotomy (CE) groups. Enterotomy construction and leak testing were performed within 12 h of euthanasia for the C and FE groups and after 17-29 h of cooling for the CE group. Initial leak pressure (ILP) and maximum intraluminal pressure (MIP) were compared. Gastrointestinal wall thickness and intraluminal diameter were measured on harvested applicable gastrointestinal divisions at up to three time points: day 1 fresh, day 2 cooled, and day 3 cooled. RESULTS: The mean (± SD) ILPs for the C, FE, and CE constructs were 600 (± 0.0), 200.3 (± 114.7), and 131.3 (± 92.6) mmHg, respectively. The C ILP was higher (p < .001) than the FE and CE ILP. The ILP (p = .11) and the MIP (p = .21) did not differ between the FE and CE constructs. Wall thickness (measured in mm) did not differ between duodenum day 1 fresh and day 2 cooled groups (p = .18) or between any jejunum day groups (p = .86). The intraluminal diameters (mean ± SD) for the duodenum, jejunum, and ileum were 5.7 (± 0.7), 5.8 (± 0.8), and 7.2 (± 2.2) mm, respectively. CONCLUSION: No difference was appreciated between FE and CE ILP and MIP. Wall thickness measurements did not differ between days for duodenum or jejunum. CLINICAL RELEVANCE: Cadaveric feline intestine cooled for up to 29 h may be used for determining intestinal leak pressures.

Vagus nerve damage increases alcohol intake and preference in a nonpreferring rat line: Relationship to vagal regulation of the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Clinical and preclinical research indicates that gastric weight loss surgeries, such as Roux-en-Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake. METHODS: To test this hypothesis, we compared alcohol intake and preference in multiple models in male Sprague-Dawley rats that received selective gastric branch vagotomy (VX) with rats who underwent sham surgery. Because the vagus nerve regulates hypothalamic-pituitary-adrenal (HPA) axis function, and alterations to HPA function are critical to the escalation of non-dependent alcohol intake, we also tested the hypothesis that gastric VX increases HPA function. RESULTS: We found that VX increases alcohol intake and preference in the every-other-day, two-bottle choice test and increases preference for 1 g/kg alcohol in the conditioned place preference test. The effects were selective for alcohol, as sucrose intake and preference were not altered by VX. We also found that VX increases corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN), increases putative PVN CRF neuronal action potential firing, and increases corticosterone levels. CONCLUSIONS: Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of PVN CRF mRNA expression and putative PVN CRF neuronal activity. Furthermore, disruptions to vagal regulation of HPA axis function may increase alcohol intake and preference.

Predictors of Semen Parameters Decline Following the Microsurgical Varicocelectomy.

Objective Varicocele is considered the most common reversible cause of male infertility. However, some men do not clinically improve after surgical repair. We aimed to identify preoperative factors associated with decreased semen parameters and clinical "downgrading" of total motile sperm count (TMSC) following varicocelectomy. Methods We examined men with preoperative laboratory testing and pre- and postoperative semen analyses (SA) who underwent varicocelectomy between 2010 and 2020. Ejaculate volume, sperm motility, sperm concentration, TMSC, and clinical grade of TMSC (in vitro fertilization: <5M sperm, intrauterine insemination: 5-9M sperm, natural pregnancy: >9M sperm) were used to determine postoperative outcomes. Demographic and clinical factors were compared between cohorts. Results Among 101 men who underwent varicocelectomy, 35 (34.7%) had decreased postoperative TMSC with a median follow-up of 6.6 months (interquartile range 3.9-13.6 months). Eleven (10.9%) men experienced TMSC clinical "downgrading" following surgery. Clinical grade III varicocele was significantly associated with decreased sperm motility on postoperative SA (OR 4.1, 95% CI 1.7-10.0, p=0.002), and larger left testicle volume (OR 1.4, 95% CI 1.1-1.8, p=0.02) was associated with clinical "downgrading" after varicocelectomy. Conclusion A small but significant proportion of men experienced a "downgrading" of semen parameters after varicocelectomy. Larger left testis size was associated with clinical downgrading, whereas clinical grade III varicoceles were associated with lower post-treatment sperm motility. These data are critical for preoperative patient counseling.

Effects of feeding high oleic soybean oil to growing-finishing pigs on loin and belly quality.

Feeding growing-finishing pigs supplemental fat is a common practice in the swine industry and can result in improved feed efficiency and reduced feed intake; however, dietary lipids also play a key role in determining pork quality. Objectives of the study were to evaluate the effects of feeding graded levels of high oleic soybean oil (HOSO) on loin and belly quality. A total of 288 pig raised in two separate blocks (144 pigs each) were assigned to one of four diets containing either 25% dried distiller's grains with solubles (DDGS), 2% high oleic soybean oil (HOSO2), 4% high oleic soybean oil (HOSO4), or 6% high oleic soybean oil (HOSO6). Following the conclusion of the feeding trial, 144 pigs were slaughtered at the University of Illinois Meat Science Laboratory. Following fabrication, loins were collected for the evaluation of fresh quality measurements and color stability. Belly quality and fatty acid composition were evaluated using skin-on natural fall bellies. There were no differences (P ≥ 0.11) in pH, visual color, lightness (L*), drip loss, or WBSF among dietary treatments. However, visual marbling was increased (P ≤ 0.01) in loin chops from pigs fed HOSO4 and HOSO6 treatments compared with chops from pigs fed the DDGS dietary treatment. Additionally, loin chops were more red (a*) (P ≤ 0.01) from pigs fed HOSO diets when compared with pigs fed DDGS. Extractable lipid was decreased (P ≤ 0.01) in fresh loin chops from pigs fed DDGS and HOSO2 diets compared with pigs fed HOSO6. There were no differences (P ≥ 0.75) in trained sensory tenderness, juiciness, or flavor for loin chops from pigs fed different dietary treatments. Pork fatty acid composition was altered by dietary HOSO inclusion, with pigs fed DDGS having (P ≤ 0.01) the greatest concentration of C16:0 and was decreased with increasing levels of HOSO inclusion. Inversely, the percentage of C18:1n-9 was least (P ≤ 0.01) in pigs fed DDGS and increased with increasing levels of HOSO inclusion. Pigs fed DDGS produced wider (P ≤ 0.03) and thinner (P ≤ 0.04) bellies with reduced flop distance compared with pigs fed HOSO diets. Overall, HOSO diets did not negatively affect fresh loin quality or sensory traits of loin chops. Furthermore, feeding HOSO to swine resulted in bellies containing greater percentages of oleic acid and reduced percentages of palmitic and linoleic acid.

Feeding pigs supplemental fat to increase caloric density is a common practice in the swine industry. However, dietary fats are also a key determinant of pork fat composition and may influence product quality. High oleic soybean oil (HOSO), a relatively new feed ingredient, differs from conventional soybean oil in that it contains an increased proportion of oleic acid, a monounsaturated fatty acid. However, HOSO has not been extensively researched in pig diets. Therefore, our goal was to investigate the use of dietary HOSO on fresh belly and loin quality. A total of 144 pigs, fed one of four diets that differed in fat source, were slaughtered at the University of Illinois Meat Science Laboratory. One diet contained 25% dried distiller's grains with solubles (DDGS), while the other three had graded levels of high oleic soybean oil (2%, 4%, or 6%). Pigs were fed diets for the last 14 weeks leading up to slaughter. Pigs fed HOSO produced thicker, firmer bellies and fat tissue containing a decreased proportion of polyunsaturated fatty acids compared with DDGS-fed pigs. Feeding HOSO had little impact on fresh loin quality and palatability compared with feeding an industry-reference diet containing DDGS.

Effects of feeding high oleic soybean oil to growing-finishing pigs on growth performance and carcass characteristics.

Feeding growing-finishing pigs supplemental fat is a common practice in the swine industry and can result in improved feed efficiency and reduced feed intake; however, dietary lipids also play a key role in determining pork composition. The objectives of the current study were to evaluate the effects of feeding graded levels of high oleic soybean oil (HOSO) on growth performance and carcass characteristics. A total of 288 pigs raised in two separate blocks (144 pigs each) were assigned to one of four diets containing either 25% dried distiller's grains with solubles (DDGS), 2% high oleic soybean oil (HOSO2), 4% high oleic soybean oil (HOSO4), or 6% high oleic soybean oil (HOSO6). Pigs were housed 4 per pen and fed for 98 d using a 3-phase feeding system. Pigs were individually weighed and feed intake was recorded throughout the trial to calculate average daily feed intake (ADFI) and gain to feed ratio (G:F). A total of 144 pigs were transported to the University of Illinois Meat Science Laboratory and fabricated into primal and subprimal cuts to calculate carcass cutting yields. Differences in growth performance were observed, with pigs fed the DDGS treatment exhibiting greater (P ≤ 0.01) overall ADFI consuming 0.21, 0.18, and 0.28 kg/d more than HOSO2, HOSO4, and HOSO6 diets, respectively. Pigs fed the HOSO6 diet had greater (P ≤ 0.03) overall G:F than pigs fed DDGS and HOSO2 diets but did not differ (P = 0.12) from pigs fed HOSO4. Furthermore, differences in carcass traits were observed. Hot carcass weight was increased (P ≤ 0.03) in pigs fed the HOSO6 diet compared with pigs fed the DDGS and HOSO2 diets, while pigs fed HOSO4 did not differ (P > 0.05) from either extreme. Additionally, pigs fed HOSO4 and HOSO6 produced fatter (P ≤ 0.01) carcasses with reduced (P ≤ 0.01) standardized fat-free lean. Minimal differences were observed in primal weights expressed as a percentage of chilled side including bone-in Boston butt, trimmed loin, and trimmed ham with primal weights decreasing with increasing inclusion of dietary HOSO. Overall, pigs fed HOSO2 had reduced ADFI with similar backfat thickness and standardized fat-free lean compared with pigs fed the DDGS treatment. However, pigs fed HOSO 4% and 6% not only had improvements in ADFI and G:F but also had increased backfat thickness, which resulted in reductions in standardized fat-free lean and primal weights expressed as a percentage of chilled side weight.

Feeding pigs supplemental fat to increase caloric density is a common practice in the swine industry and can result in improved feed efficiency. However, high oleic soybean oil (HOSO), a relatively new feed ingredient, has not been extensively researched in pig diets. HOSO differs from conventional soybean oil in that it contains an increased proportion of oleic acid, a monounsaturated fatty acid. Therefore, our goal was to investigate the use of HOSO in the diets of pigs in the weeks leading up to marketing. A total of 288 pigs were fed one of four diets that differed in their source of fat. One diet contained 25% dried distiller's grains with solubles (DDGS), while the other three had graded levels of HOSO (2%, 4%, or 6%). Pigs were fed diets for the last 14 wk leading up to slaughter. Pigs fed the highest level of HOSO grew more efficiently and were heavier than those fed the diet containing DDGS. However, pigs fed 6% HOSO were also fatter and yielded a reduced percentage of boneless meat cuts than those fed DDGS.

Estimating the price elasticity of demand for JUUL E-cigarettes among teens.

BACKGROUND: The widespread popularity of e-cigarettes, particularly JUUL, has led to an alarming increase in teen nicotine use, reversing a 40-year trend. One key question is how sensitive teens' demand for JUUL is to changes in price. METHODS: We estimate the price elasticity of demand using results from an experimental auction where teen nicotine users and nonusers bid on a JUUL kit. RESULTS: We find that a 10 % increase in price leads to as much as a 24 % reduction in JUUL demand among teens using nicotine, and as much as a 45 % reduction among teens not currently using nicotine. The teens in our study were more price sensitive than older adults who took part in a similar earlier study. CONCLUSIONS: From a public health standpoint, these are promising results. High e-cigarette taxes may dissuade relatively few older adult cigarette smokers from switching to e-cigarettes, but at the same time be highly effective at preventing teens from becoming e-cigarette users in the first place.

NEDD9 stimulated MMP9 secretion is required for invadopodia formation in oral squamous cell carcinoma.

Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a component of the metastatic signatures of melanoma, breast cancer, glioblastoma, lung cancer and head and neck squamous cell carcinoma (HNSCC). Here we tested the efficacy of NEDD9's domains in stimulating matrix metalloproteinase (MMP) secretion and invadopodia formation in cells stably expressing various NEDD9 mutants. Replacement of the 13 YxxP motif substrate domain (SD) tyrosines and the C-terminal Y629 with phenylalanines (F14NEDD9) eliminated tyrosine phosphorylation, MMP9 secretion and loss of invadopodia formation. Mutation of the N-terminal SH3 domain Y12 to glutamic acid (Y12ENEDD9) or phenylalanine (Y12FNEDD9) reduced MMP9 secretion and inhibited invadopodia formation. SH3 domain deletion (∆SH3NEDD9) resulted in the loss of MMP9 secretion and a lack of invadopodia formation. The SH3-SD domain (SSNEDD9) construct exhibited tyrosine phosphorylation and stimulated MMP9 secretion, as did ∆CTNEDD9 which lacked the C-terminus (∆C-terminal; ∆CT). E13NEDD9 expression blocked MMP9 secretion and invadopodia formation. MICAL1 (molecule interacting with Cas-L1) silencing with a short hairpin RNA reduced MMP9 secretion, vimentin and E-cadherin levels while increasing N-cadherin and Rab6 levels, consistent with reduced invasive behavior. These findings indicate that NEDD9 SD phosphorylation and SH3 domain interactions are necessary for increasing MMP9 secretion and invadopodia formation.

Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer.

Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2), stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity.

AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.

Biochemical and structural characterization of Pseudomonas aeruginosa Bfd and FPR: ferredoxin NADP+ reductase and not ferredoxin is the redox partner of heme oxygenase under iron-starvation conditions.

Among the 118 genes upregulated by Pseudomonas aeruginosa in response to iron starvation [Ochsner, U. A., Wilderman, P. J., Vasil, A. I., and Vasil, M. L. (2002) Mol. Microbiol. 45, 1277-1287], we focused on the products of the two genes encoding electron transfer proteins, as a means of identifying the redox partners of the heme oxygenase (pa-HO) expressed under low-iron stress conditions. Biochemical and spectroscopic investigations demonstrated that the bfd gene encodes a 73-amino acid protein (pa-Bfd) that incorporates a [2Fe-2S]2+/+ center, whereas the fpr gene encodes a 258-residue NADPH-dependent ferredoxin reductase (pa-FPR) that utilizes FAD as a cofactor. In vitro reconstitution of pa-HO catalytic activity with the newly characterized proteins led to the surprising observation that pa-FPR efficiently supports the catalytic cycle of pa-HO, without the need of a ferredoxin. In comparison, electron transfer from pa-Bfd to pa-HO is sluggish, which strongly argues against the possibility that the seven electrons needed by pa-HO to degrade biliverdin are transferred from NADPH to pa-HO in a ferredoxin (Bfd)-dependent manner. Given that pa-HO functions to release iron from exogenous heme acquired under iron-starvation conditions, the use of a flavoenzyme rather than an iron-sulfur center-containing protein to support heme degradation is an efficient use of resources in the cell. The crystal structure of pa-FPR (1.6 A resolution) showed that its fold is comparable that of the superfamily of ferredoxin reductases and most similar to the structure of Azotobacter vinelandii FPR and Escherichia coli flavodoxin reductase. The latter two enzymes interact with distinct redox partners, a ferredoxin and a flavodoxin, respectively. Hence, findings reported herein extend the range of redox partners recognized by the fold of pa-FPR to include a heme oxygenase (pa-HO).

Heme oxidation in a chimeric protein of the alpha-selective Neisseriae meningitidis heme oxygenase with the distal helix of the delta-selective Pseudomonas aeruginosa.

Heme oxygenases from the bacterial pathogens Neisseriae meningitidis (nm-HO) and Pseudomonas aeruginosa (pa-HO) share significant sequence identity (37%). In nm-HO, biliverdin IXalpha is the sole product of the reaction, whereas pa-HO yields predominantly biliverdin IXdelta. We have previously shown by NMR that the in-plane conformation of the heme in pa-HO is significantly different from that of nm-HO as a result of distinct interactions of the heme propionates with the protein scaffold [Caignan, G. A., Deshmukh, R., Wilks, A., Zeng, Y., Huang, H. W., Moenne-Loccoz, P., Bunce, R. A., Eastman, M. A., and Rivera, M. (2002) J. Am. Chem. Soc. 124, 14879-14892]. In the report presented here, we have extended these studies to investigate the role of the distal helix by preparing a chimera of nm-HO (nm-HOch), in which distal helix residues 107-142 of nm-HO have been replaced with the corresponding residues of the delta-regioselective pa-HO (112-147). Electronic absorption spectra, resonance Raman and FTIR spectroscopic studies confirm that the orientation and hydrogen bonding properties of the proximal His ligand are not significantly altered in the chimera relative those of the wild-type proteins. The catalytic turnover of the nm-HOch-heme complex yields almost exclusively alpha-biliverdin and a small but reproducible amount of delta-biliverdin. NMR spectroscopic studies reveal that the altered regioselectivity in the chimeric protein likely stems from a dynamic equilibrium between two alternate in-plane conformations of the heme (in-plane heme disorder). Replacement of K16 with Ala and Met31 with Lys in the chimeric protein in an effort to tune key polypeptide-heme propionate contacts largely stabilizes the in-plane conformer conducive to delta-meso hydroxylation.

Are solitary and gregarious Mormon crickets (Anabrus simplex, Orthoptera, Tettigoniidae) genetically distinct?

Phase polyphenisms are usually thought to reflect plastic responses of species, independent of genetic differences; however, phase differences could correlate with genetic differentiation for various reasons. Mormon crickets appear to occur in two phases that differ in morphology and behaviour. Solitary individuals are cryptic and sedentary whereas gregarious individuals form bands, migrate, and are aposematically coloured. These traits have been thought to be phenotypically plastic and induced by environmental conditions. However, there has been no previous investigation of the extent of genetic differences between solitary and gregarious populations of this widespread North American species. We sequenced two mitochondrial genes, COII and COIII, in samples of Mormon crickets from gregarious populations west of the continental divide and solitary mountain populations primarily east of the divide. Sequencing revealed two genetically distinct clades that broadly correspond with the solitary eastern populations and the mainly gregarious western populations. We used coalescent modelling to test the hypothesis that the species consists of two deep genetic clades, as opposed to a series of equally distinct populations. Results allowed us to reject the null hypothesis that a radiation independent of phase produced these clades, and molecular clock estimates indicate the time of divergence to be approximately 2 million years ago. This work establishes that the solitary populations found in the mountains on the eastern slope are part of a clade that is genetically distinct from the western populations, which are primarily gregarious, and the implications of this apparent correlation between phase and genetic differentiation are discussed.

Coronary revascularization in heart transplant recipients by excimer laser angioplasty.

BACKGROUND AND OBJECTIVE: Aggressive development of allograft coronary artery disease is a major cause of death in heart transplant recipients. Percutaneous balloon angioplasty is considered suboptimal for complex lesions in native coronary vessels and heart transplant recipients, alike. Excimer laser energy (308-nm wavelength) can successfully remove and vaporize atherosclerotic plaques in native coronary vessels; however, its application in heart transplant recipients has not been studied clinically yet. STUDY DESIGN/MATERIALS AND METHODS: Six heart transplant recipients underwent percutaneous excimer laser (CVX-300, Spectranetics, Colorado Springs, CO) coronary angioplasty for treatment of a total of 10 discrete, obstructive coronary artery lesions. By using concentric or eccentric multifiber laser catheters, energy parameters were set at a fluence of 45 mJ/mm(2) or 60 mJ/mm(2) with a frequency of 25 Hz and 40 Hz, respectively, with a pulse duration of 135 ns and output of 200 mJ/pulse. The "saline flush" and "pulse and retreat" lasing techniques were used. In each case, adjunct balloon angioplasty was performed; in five lesions, an intracoronary stent was implanted. Angiographic evaluation was performed by visual assessment. RESULTS: Each procedure was successful as defined by laser recanalization of the target lesion (reduction of target lesion stenosis in more than 20%) and subsequent adequate final luminal patency (reduction of target lesion stenosis to less than 50%) and absence of any major in-cardiac catheterization complication (such as perforation, acute closure, dissection, emergency coronary artery bypass surgery), or in-hospital complications (such as death, myocardial infarction, cardiac enzyme elevation, major bleeding), or need for surgical revascularization. A 92 +/- 5% preprocedural percent diameter stenosis was reduced by laser to 35 +/- 16% and by adjunct balloon angioplasty in all lesions and stenting in five lesions, to final residual stenosis of 2 +/- 6%. Angiographic follow-up between 2 and 6 months after the procedure demonstrated a target lesion restenosis rate of 22%. CONCLUSION: Percutaneous excimer laser is safe and efficacious in the treatment of focal obstructive lesions caused by allograft coronary artery disease. These data represent an early clinical experience; thus, the long-term outcome of this revascularization method in recipients of heart transplantation will have to be determined by a large scale prospective, randomized, multicenter clinical study.

Large-scale UK audit of blood transfusion requirements and anaemia in patients receiving cytotoxic chemotherapy.

Cancer patients receiving cytotoxic chemotherapy often become anaemic and may require blood transfusions. A large-scale audit of patients with a variety of solid tumours receiving chemotherapy at 28 specialist centres throughout the UK was undertaken to quantify the problem. Data were available from 2719 patients receiving 3206 courses of cytotoxic chemotherapy for tumours of the breast (878), ovary (856), lung (772) or testis (213). Their mean age was 55 years (range 16-87). Overall, 33% of patients required at least one blood transfusion but the proportion varied from 19% for breast cancer to 43% for lung. Sixteen per cent of patients required more than one transfusion (7% for breast, 22% in lung). The mean proportion of patients with Hb < 11 g dl(-10 rose over the course of chemotherapy from 17% before the first cycle, to 38% by the sixth, despite transfusion in 33% of patients. Of the patients receiving transfusions, 25% required an inpatient admission and overnight stay. The most common symptoms reported at the time of transfusion were lethargy, tiredness and breathlessness. Further research is needed to evaluate the role of blood transfusions in patients receiving cytotoxic chemotherapy.

Carboplatin and paclitaxel, alone and in combination: dose escalation, measurement of renal function, and role of the p53 tumor suppressor gene.

In this pharmacokinetic and dose-escalation study of the carboplatin/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combination, patients were randomly assigned to receive paclitaxel either as a 1-hour or a 3-hour infusion. The 1-hour infusion was feasible, with maximum tolerated doses similar to those previously reported for a 3-hour infusion. Using patients' age, height, plasma creatinine, and plasma creatine kinase provided an improved estimate of the glomerular filtration rate compared with the more traditional creatinine-based formulas according to population analysis of data derived from glomerular filtration rate estimates performed by an isotope method. Studies of the p53 gene sequence of ovarian tumors at diagnosis suggest that p53 mutations are a potent predictor of response to subsequent treatment with carboplatin.