Surgical Pulmonary Embolectomy: Experience in a Series of 37 Consecutive Cases.

BACKGROUND: Massive pulmonary embolism is a poorly tolerated condition. Treatment options in this condition include anticoagulation and primary reperfusion therapy - systemic thrombolysis, catheter based treatments or surgical embolectomy. There is little data on the relative efficacy of each treatment. METHODS: The preoperative characteristics and outcomes of patients referred for surgical embolectomy between 2000-2014 was reviewed. Echocardiography was performed in the majority of patients before and after surgery. RESULTS: Thirty-seven patients underwent pulmonary embolectomy between 2000-2014. One patient died within 30 days, another before leaving hospital. All other patients were alive at the time of follow-up (survival 94.6% at median 36 months). Median ventilation time was 24hours. Median hospital length of stay was 10.5 days. There was echocardiographic evidence of severe right ventricular strain (increased size and decreased function) before surgery, which was significantly improved to within the normal range by discharge, and follow-up. CONCLUSIONS: Surgical embolectomy is a safe procedure, with low mortality, improved postoperative right ventricular function and pulmonary pressure, and good long-term outcome. Early relief of a large proportion of the clot burden can be life-saving. There should be consideration for its use as an initial treatment strategy in patients with massive or submassive pulmonary embolus with a large burden of proximal clot. A multidisciplinary approach for the treatment of these patients is required.

First Report of the Soybean Frogeye Leaf Spot Fungus (Cercospora sojina) Resistant to Quinone Outside Inhibitor Fungicides in North America.

Quinone outside inhibitor (QoI; also known as strobilurin) fungicides sometimes are applied to soybean (Glycine max) fields to help manage frogeye leaf spot of soybean (caused by Cercospora sojina) in the United States. In August 2010, soybean leaflets exhibiting severe frogeye leaf spot symptoms were collected from a field in Lauderdale County, TN that had been treated twice with pyraclostrobin during that growing season. The field had been planted into soybean annually since at least 2008, and a QoI fungicide had been applied to the field in each of those years. Fifteen single-spore isolates of C. sojina were recovered from the affected soybean leaflets. These isolates were identified as C. sojina based on the observed symptoms on the soybean leaflets and the morphology and size of conidiophores and conidia (3). In addition, DNA was extracted from the cultures, PCR amplification of the small subunit rDNA and internal transcribed spacer (ITS) region was conducted (2), and the resulting PCR product was sequenced at the Keck Biotechnology Center at the University of Illinois, Urbana. The resulting nucleotide sequences were compared with sequences deposited in the nucleotide database ( http://www.ncbi.nlm.nih.gov ) and showed highest homology to sequences of C. sojina. The isolates were tested for their sensitivity to technical-grade formulations of the QoI fungicides azoxystrobin, pyraclostrobin, and trifloxystrobin with an in vitro conidial germination assay with fungicide + salicylhydroxamic acid (SHAM)-amended potato dextrose agar as described by Bradley and Pedersen (1). The effective concentration at which 50% conidial germination was inhibited (EC50) was determined for all 15 C. sojina isolates, with mean values of 3.1644 (2.7826 to 4.5409), 0.3297 (0.2818 to 0.6404), and 0.8573 (0.3665 to 2.5119) µg/ml for azoxystrobin, pyraclostrobin, and trifloxystrobin, respectively. When compared with previously established mean EC50 values of C. sojina baseline isolates (4), EC50 values of the C. sojina isolates collected from the Lauderdale County, TN soybean field were approximately 249- to 7,144-fold greater than the EC50 values of the baseline isolates. These results indicate that all isolates recovered from the Lauderdale County, TN soybean field were highly resistant to QoI fungicides. To our knowledge, this is the first report of QoI fungicide resistance occurring in C. sojina, and surveys for additional QoI fungicide-resistant C. sojina isolates are needed to determine their prevalence and geographic distribution. In light of these findings, soybean growers in Tennessee and adjacent states should consider utilizing alternative frogeye leaf spot management practices such as planting resistant cultivars, rotating to nonhost crops, and tilling affected soybean residue (3). References: (1) C. A. Bradley and D. K. Pedersen. Plant Dis. 95:189, 2011. (2) N. S. Lord et al. FEMS Microbiol. Ecol. 42:327, 2002. (3) D. V. Phillips. Page 20 in: Compendium of Soybean Diseases. 4th ed. G. L. Hartman et al., eds. The American Phytopathological Society, St. Paul, MN, 1999. (4) G. Zhang et al. Phytopathology (Abstr.) 100(suppl.):S145, 2010.

Importance of Fungicide Seed Treatment and Environment on Seedling Diseases of Cotton.

The importance of fungicide seed treatments on cotton was examined using a series of standardized fungicide trials from 1993 to 2004. Fungicide seed treatments increased stands over those from seed not treated with fungicides in 119 of 211 trials. Metalaxyl increased stands compared to nontreated seed in 40 of 119 trials having significant fungicide responses, demonstrating the importance of Pythium spp. on stand establishment. Similarly, PCNB seed treatment increased stands compared to nontreated seed for 44 of 119 trials with a significant response, indicating the importance of Rhizoctonia solani in stand losses. Benefits from the use of newer seed treatment chemistries, azoxystrobin and triazoles, were demonstrated by comparison with a historic standard seed treatment, carboxin + PCNB + metalaxyl. Little to no stand improvement was found when minimal soil temperatures averaged 25°C the first 3 days after planting. Stand losses due to seedling pathogens increased dramatically as minimal soil temperatures decreased to 12°C and rainfall increased. The importance of Pythium increased dramatically as minimal soil temperature decreased and rainfall increased, while the importance of R. solani was not affected greatly by planting environment. These multi-year data support the widespread use of seed treatment fungicides for the control of the seedling disease complex on cotton.

Lipopolysaccharides and plant innate immunity.

Plants posses an innate immune system that has many parallels with those found in mammals and insects. A range of molecules of microbial origin called Microbe Associated Molecular Patterns (MAMPs) act to trigger basal defense responses in plants. These elicitors include lipopolysaccharides (LPS) from diverse Gram-negative bacteria. Both core oligosaccharide and the lipid A moieties of LPS as well as synthetic O-antigen oligosaccharides have activity in inducing defense responses in the model plant Arabidopsis thaliana. Very little is known of the mechanism of LPS perception by plants, although plant receptors for other MAMPs such as flagellin have been described. Recent work has implicated the Arabidopsis syntaxin PEN1 as a potential actor in LPS induction of plant defenses, which may suggest a role for vesicle trafficking in the signalling process.

Biological monitoring screening of patients provided antineoplastic drugs including adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate, and vincristine.

The aim of the present study was to establish screening biomarkers of exposure to antineoplastic drugs administered to 11 patients undergoing cancer chemotherapy. Among the anticancer drugs administered were cyclophosphamide (all), Adriamycin (5 of 11), methotrexate (3 of 11), 5-fluorouracil (4 of 11), vincristine (3 of 11), megestrol acetate (1 of 11), and procarbazine (1 of 11). The noninvasive urinary parameters investigated were thioethers, D-glucaric acid, elements, and forward and reverse mutagenesis using bacterial bioassays. The data were analyzed in terms of the observed concentrations and those corrected for personal baseline. Personal baseline correction for parameters with significant nonexposure baseline levels was essential. While glucaric acid and thioethers were increased by the drug treatments, the correlations with baseline-uncorrected data showing an inverse relationship proved spurious, because saturation of the detoxification systems occurred at the high doses administered. Glucaric acid was also influenced by methotrexate and vincristine. Thioether content was affected by cyclophosphamide only. The forward mutagenesis assay was directly correlated to cyclophosphamide dose but the reverse assay was not, in the presence or absence of rat S9 fraction. The forward assay was not sensitive to the effects of smoking. Relative to controls, the elements changed by cyclophosphamide were K, S, and P. Those affected by Adriamycin were Ca, Mg, and Na; 5-fluorouracil affected Ca, Mg, Na, and C; methotrexate changed P and S. The forward mutagenesis assay and D-glucaric acid concentrations were the screening biomarkers best suited to monitoring for extent of exposure to these antineoplastic drugs.

Defining the physical properties of corn grown under drought-stressed conditions and the associated energy and nutrient content for swine.

Historically high temperatures and low rainfall during the 2012 growing season resulted in drought-stressed conditions in much of the U.S. corn belt. The objective of this experiment was to investigate the impact of these conditions on the composition and energy content in corn and determine if relationships exist among corn quality measurements, chemical composition, and digestibility of energy. Twenty-eight samples of corn from the 2012 drought-stressed crop (DS), plus 2 representative corn samples from the 2011 crop (CNTRL), were collected in Iowa and Illinois using yield as an initial screen for drought impact. Yields ranged from 2.5 to 14.8 t/ha. Each sample was graded by an official of the U.S. grain inspection agency and analyzed for 1,000 kernel weight, kernel density, ether extract, starch, GE, NDF, and CP content. Diets were formulated using each of the 30 corn samples and were fed at 2.6 times the estimated maintenance energy requirement according to the . Sixty individually housed barrows (PIC 359 × C29; 34.2 ± 0.2 kg initial BW) were randomly allotted in an incomplete crossover design to 30 diets across 4 periods. Diet and fecal samples were analyzed to determine DE values. Both ME and NE values were then calculated from DE values using methods developed by and , respectively. Mean DE, ME, and NE values between the CNTRL and DS were not different (3.72 vs. 3.68 Mcal/kg, respectively, 3.66 vs. 3.62 Mcal/kg, respectively, and 2.92 vs. 2.87 Mcal/kg, respectively; > 0.10). Comparing CNTRL with DS, there were no differences ( > 0.10) in ether extract (4.07 vs. 3.96%), CP (8.56 vs. 9.18%), or starch (70.5 vs. 69.5%). However, ADF and NDF were higher in the DS (2.23 and 8.19%, respectively) when compared with CNTRL (1.89 and 6.92%, respectively; < 0.001 and = 0.015, respectively). Small but significant correlations were observed between DE and NDF ( = -0.51, = 0.008), kernel density ( = 0.51, = 0.007), and percent damaged kernels ( = 0.41, = 0.031). No statistically significant correlations were observed between DE and starch or ADF content or between DE and test weight. We can conclude that corn grown in drought-stressed conditions has energy content similar to corn grown under more favorable conditions and, therefore, can be successfully used in swine diets. Furthermore, NDF proved to be superior to fat, starch, and ADF content in explaining the variation in corn energy content.

Enzymatically Modified Starch Favorably Modulated Intestinal Transit Time and Hindgut Fermentation in Growing Pigs.

Aside from being used as stabilizing agents in many processed foods, chemically modified starches may act as functional dietary ingredients. Therefore, development of chemically modified starches that are less digestible in the upper intestinal segments and promote fermentation in the hindgut receives considerable attention. This study aimed to investigate the impact of an enzymatically modified starch (EMS) on nutrient flow, passage rate, and bacterial activity at ileal and post-ileal level. Eight ileal-cannulated growing pigs were fed 2 diets containing 72% purified starch (EMS or waxy cornstarch as control) in a cross-over design for 10 d, followed by a 4-d collection of feces and 2-d collection of ileal digesta. On d 17, solid and liquid phase markers were added to the diet to determine ileal digesta flow for 8 h after feeding. Reduced small intestinal digestion after the consumption of the EMS diet was indicated by a 10%-increase in ileal flow and fecal excretion of dry matter and energy compared to the control diet (P<0.05). Moreover, EMS feeding reduced ileal transit time of both liquid and solid fractions compared to the control diet (P<0.05). The greater substrate flow to the large intestine with the EMS diet increased the concentrations of total and individual short-chain fatty acids (SCFA) in feces (P<0.05). Total bacterial 16S rRNA gene abundance was not affected by diet, whereas the relative abundance of the Lactobacillus group decreased (P<0.01) by 50% and of Enterobacteriaceae tended (P<0.1) to increase by 20% in ileal digesta with the EMS diet compared to the control diet. In conclusion, EMS appears to resemble a slowly digestible starch by reducing intestinal transit and increasing SCFA in the distal large intestine.

Disruption of the helix-u-turn-helix motif of MutS protein: loss of subunit dimerization, mismatch binding and ATP hydrolysis.

The DNA mismatch repair protein, MutS, is a dimeric protein that recognizes mismatched bases and has an intrinsic ATPase activity. Here, a series of Taq MutS proteins having C-terminal truncations in the vicinity of a highly conserved helix-u-turn-helix (HuH) motif are assessed for subunit oligomerization, ATPase activity and DNA mismatch binding. Those proteins containing an intact HuH region are dimers; those without the HuH region are predominantly monomers in solution. Steady-state kinetics of truncated but dimeric MutS proteins reveals only modest decreases in their ATPase activity compared to full-length protein. In contrast, disruption of the HuH region results in a greatly attenuated ATPase activity. In addition, only dimeric MutS proteins are proficient for mismatch binding. Finally, an analysis of the mismatch repair competency of truncated Escherichia coli MutS proteins in a rifampicin mutator assay confirms that the HuH region is critical for in vivo function. These findings indicate that dimerization is critical for both the ATPase and DNA mismatch binding activities of MutS, and corroborate several key features of the MutS structure recently deduced from X-ray crystallographic studies.

Lipopolysaccharide from Xanthomonas campestris induces defense-related gene expression in Brassica campestris.

Purified lipopolysaccharide (LPS) from Xanthomonas campestris pv. campestris induced accumulation of transcript for beta-1,3-glucanase in turnip at concentrations of 1 micrograms/ml. The lipid A-inner core structure was required for activity but the O-antigen had no role. We suggest that release of LPS in planta triggers expression of at least some defense-related genes.

The activity of lipid A and core components of bacterial lipopolysaccharides in the prevention of the hypersensitive response in pepper.

Pre-treatment of leaves of pepper (Capsicum annuum) with lipopolysaccharide (LPS) preparations from enteric bacteria and Xanthomonas campestris could prevent the hypersensitive response caused by an avirulent X. campestris strain. By use of a range of deep-rough mutants, the minimal structure in Salmonella LPS responsible for the elicitation of this effect was determined to be lipid A attached to a disaccharide of 2-keto-3-deoxyoctulosonate; lipid A alone and the free core oligosaccharide from a Salmonella Ra mutant were not effective. For Xanthomonas, the core oligosaccharide alone had activity although lipid A was not effective. The results suggest that pepper cells can recognize different structures within bacterial LPS to trigger alterations in plant response to avirulent pathogens.

Induction of hydroxycinnamoyl-tyramine conjugates in pepper by Xanthomonas campestris, a plant defense response activated by hrp gene-dependent and hrp gene-independent mechanisms.

Inoculation of pepper leaves, Capsicum annuum cv. Early Calwonder ECW 10R, with strains of Xanthomonas campestris led to an accumulation of the phenolic conjugates feruloyltyramine (FT) and p-coumaroyltyramine (CT) 24 h postinoculation in nonhost- and gene-for-gene-determined incompatible interactions with X. campestris pv. campestris and X. campestris pv. vesicatoria, respectively. In contrast, neither compound was detected in compatible interactions with X. campestris pv. vesicatoria. The accumulation of FT and CT was preceded by an increase in the extractable activity of tyrosine decarboxylase as well as increases in the transcription of genes encoding phenylalanine ammonia-lyase and tyramine hydroxycinnamoyl transferase. No such changes were detected in compatible interactions. Very rapid accumulation of FT and CT occurred (4 h postinoculation) in pepper in response to a X. campestris pv. campestris mutant carrying a deletion of the hrp gene cluster. In contrast, hrp mutants of X. campestris pv. vesicatoria failed to elicit the production of FT and CT. These observations suggest the existence of hrp gene-dependent and -independent activation mechanisms of a defense response involving hydroxycinnamoyltyramines.

Defense-related gene induction in Brassica campestris in response to defined mutants of Xanthomonas campestris with altered pathogenicity.

We have studied the induction of beta-1,3-glucanase (BGL) in turnip following inoculation with pathovars of Xanthomonas campestris and derived mutants. BGL transcript accumulated more rapidly in leaves in the incompatible interactions with X. c. pv. armoraciae and X. c. pv. raphani than in the compatible interaction with X. c. pv. campestris. No accumulation was seen in response to wounding or inoculation with water, salicylic acid, or Escherichia coli. Deletion of the hrp cluster from the X. campestris pathovars caused a reduction in the level of transcript accumulation; these effects were much more pronounced in the incompatible than in the compatible interaction, in which bacterial growth was also affected. In the compatible interaction, bacterial growth and BGL transcript accumulation were not altered by mutation of bacterial genes involved in the regulation of the synthesis of extracellular enzymes or their export from the cell, or by mutation of the structural genes for extracellular endoglucanase and serine protease. Mutation of genes involved in the synthesis of extracellular polysaccharide or lipopolysaccharide reduced bacterial survival in planta, so that the numbers were between two and three orders of magnitude lower than the number of wild-type bacteria. However, total BGL transcript accumulation after inoculation with these mutants was about 80% of that seen after inoculation with the wild-type bacteria, suggesting that one aspect of the role of extracellular polysaccharide and lipopolysaccharide in pathogenesis is to mask the presence of bacteria in the plant. Our results are discussed in the context of work on other plant-microbe interactions.

Near-drowning complicated by brain abscess due to Petriellidium boydii.

Extracutaneous infection from Petriellidium boydii is an unusual occurrence despite the ubiquity of the organism in nature. Central nervous system infection by this organism is extremely rare, only seven previous reports having been found. The rarity of this manifestation prompted the report of a brain abscess occurring in a previously healthy youth after a near-drowning. The source of the infection was likely to have been the river water at the accident site, from which P boydii was isolated. Although previous in vitro susceptibility data and failure of amphotericin B therapy in a similar infection suggested miconazole treatment might be beneficial, the organism causing the brain abscess was resistant to miconazole and amphotericin B. This report emphasizes the urgent need for safer and more predictably effective alternatives to currently available antifungal agents.

Polyclonal rabbit antisera that detect the Vpr protein of SIVSM and SIVMAC on immunoblots of purified virions.

Antisera suitable for detection of SIVSM or SIVMAC Vpr proteins on Western blots of purified virions are currently not available. We have expressed the Vpr protein of SIVSMPBj1.9 in a gst-based prokaryotic expression system and used it to raise polyclonal antisera in rabbits. Two immune sera were obtained that specifically recognized both cell- and virion-associated Vpr protein on immunoblots of three different SIV isolates (SIVSMPBj1.9, SIVMACBK28, and SIVMAC239). Because Vpr is believed to play an important role in HIV/SIV replication and pathogenesis, these reagents will allow the extension of functional analyses of this protein to a broader spectrum of viruses. Both antisera and the gst-Vpr expression plasmid have been submitted to the NIAID AIDS Research and Reagent Program and are available to interested investigators.

Human T lymphocytes possess a limited in vitro life span.

The T lymphocyte offers certain theoretical advantages over other available cell types for the study of aging. Immunosenescence is a well-established part of, and may be directly relevant to, mammalian aging, and the T lymphocyte is well-characterized as to function, cell-surface antigen make-up, and other factors. However, prior efforts at studying in vitro aging of T cells have been hampered by poor reproducibility in doubling potential and the occurrence of a peculiar type of crisis. We have improved the culture conditions for long-term in vitro propagation of normal human T lymphocytes so that previously described variability between identically manipulated cultures and the crisis period have been eliminated. Analysis of the growth patterns of 109 individual cultures revealed a limited proliferative life span, with the number of cumulative population doublings corresponding to that reported for adult human fibroblasts. This accord between the in vitro life spans of two vastly different cell types lends further support to the concept of the Hayflick Limit as a general biological phenomenon.

Sensitivity of the recently infarcted heart to cardioplegic arrest. Beneficial effect of pretreatment with orotic acid.

The mortality and morbidity of cardiac operations are increased in the presence of an established, recent myocardial infarct. To help understand the mechanisms for this and to develop a therapeutic strategy, we studied the response of the recently infarcted canine heart to hypothermic cardioplegia and the effect of pretreatment with orotic acid. Orotic acid is a precursor of nucleic acids with the ability to enhance protein synthesis. In 21 greyhound dogs, a myocardial infarct was produced by ligation of the left anterior descending coronary artery. Ten of these then received oral orotic acid (100 mg/kg/day) for 4 days and 11 were untreated. A sham group of eight dogs had a thoracotomy only and therefore had normal hearts (normal group). Four days later, all dogs underwent 60 minutes of cardioplegic arrest at 28 degrees C. Before arrest, stroke work index was lower and myocardial oxygen consumption at comparable work levels was higher in both the orotic acid and untreated infarct groups than in the normal group. After arrest and reperfusion, there was a severe depression of ventricular function in the untreated infarct group, with only 18% recovery of prearrest stroke work. In the orotic acid infarct group, recovery of prearrest function (43%) was similar to that in the normal group (56%) and significantly greater than in the untreated infarct group (p less than 0.01). After reperfusion, the untreated infarct group had a lower oxygen consumption, lower myocardial levels of adenosine triphosphate and glycogen, and higher lactate and water contents than before arrest (all p less than 0.05). In the orotic acid and normal groups, these variables returned to prearrest levels. We conclude that an established, recent myocardial infarct places the noninfarcted myocardium under stress and increases its sensitivity to hypothermic cardioplegia. This sensitivity is markedly reduced by treatment with orotic acid.

Evaluation of occupational asthma from airborne egg protein exposure in multiple settings.

We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.

Evaluation of a commercial exoantigen test system for the rapid identification of systemic fungal pathogens.

Seventy-nine mycelial-form stock cultures of Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and morphologically similar fungi were extracted and tested by using commercial macroimmunodiffusion exoantigen test kits and the Centers for Disease Control (CDC) reference system for identifying fungal isolates. Results showed 100% correlation between the two systems. Specific exoantigens of C. immitis and H. capsulatum extracted from agar slant cultures (slant extraction method) readily were identified. In eight of 26 cultures of B. dermatitidis, broth culture filtrates (broth-shake-flask method) were required to demonstrate the specific bands of identity. No false-negative reactions or cross-reactivity among the pathogens and other fungi were observed. The commercial test kits provided a rapid and specific method for identifying or confirming suspected fungal pathogens.

Antibiotic prophylaxis in cardiac operations.

This clinical trial, which was composed of 1,031 adults undergoing cardiac operations, compared the efficacy of a single dose of 1 g of ceftriaxone with a 48-our regimen consisting of flucloxacillin and gentamicin. There was no significant difference (p = 0.89) in the overall incidence of major infections: 30 of 515 patients (5.8%; 95% confidence interval, 5.4% to 6.2%) taking ceftriaxone and 29 of 516 patients (5.6%; 95% confidence interval, 5.2% to 6.0%) taking flucloxacillin and gentamicin. Subgroup analyses, with a lower statistical power, failed to show a significant difference between patients who received ceftriaxone and those who received flucloxacillin/gentamicin: major sternal wound infections arose in 2.7% of the patients taking ceftriaxone versus 1.6% in those on the 48-hour regimen (p = 0.20) and major limb wound infections arose in 4.2% and 5.4%, respectively (p = 0.44). Single-dose prophylaxis was associated with fewer intravenous administrations (864 doses versus 9,570 doses) and cost less (A$17,248 versus A$78,510). Although the regimen that included gentamicin was associated with the greatest biochemical impairment of renal function, the overall toxicity for both groups was low. We conclude that a single dose of ceftriaxone provided cost-efficient prophylaxis for adults undergoing cardiac operations when compared with a 48-hour regimen of gentamicin and flucloxacillin. The general principle revealed by our data is that the short-term administration of an appropriate antibiotic regimen represents optimal prophylaxis for patients undergoing cardiac procedures.

Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide.

The XAD-2 resin concentration/elution system for concentration of mutagens contained in urines was optimized for cancer patients who had been administered such antineoplastic agents as adriamycin (ADR; doxorubicin), cyclophosphamide (CP), methotrexate, vincristine, and 5-fluorouracil. In the reverse mutation assay, Salmonella typhimurium strains TA1535 and TA98 differentiated between CP (with S9 fraction) and ADR (without S9), respectively. No dose-response for CP was observed. There was a dose-response to ADR by TM677 in the presence of S9 using a forward mutation assay. However, while the reverse mutation assays successfully detected ADR and CP administration in the presence of each other in terms of urine mutagenicity, the forward mutation assay did not, since unidentified CP metabolites were also detected in the latter. None of these systems detected mutagenic urines from tobacco smokers, although reaction of these urines with beta-glucuronidase allowed this type of source to be detected also.