Children and Restraints Study in Emergency Ambulance Transport: An Observational Study and Analysis of Current Pediatric Ambulance Transport Practices.

OBJECTIVES: The aims of this study were to identify the pediatric transport methods used by Emergency Medical Services (EMS) personnel in our area and to highlight the need for federal standards to unify prehospital transport of children. METHODS: Children and Restraints Study in Emergency Ambulance Transport is a retrospective observational study of EMS arrivals to an academic pediatric emergency department for 1 year. Review of existing security footage from the ambulance entrance focused on the appropriateness of the selected restraints and the correctness of their application. A total of 3034 encounters were adequate for review and were matched to an emergency department encounter. Weight and age were identified from the chart. Patient weight was used in conjunction with video review to assess for the appropriateness of restraint selection. RESULTS: A total of 53.5% (1622) of patients were transported using a weight appropriate device or restraint system. In 77.1% of all cases (2339), the devices or restraint systems were applied incorrectly. The best results were observed for commercial pediatric restraint devices (54.5% secured appropriately) and for convertible car seats (55.5%). Ambulance cot was used alone in 69.35% of all transports despite it being the appropriate choice in just 18.2% of transports. CONCLUSIONS: Our findings confirmed that most pediatric patients transported by EMS are not appropriately secured and are at increased injury in a crash and potentially during normal vehicle operation. Opportunity exists for regulators, industry, and leaders in EMS and pediatrics to develop fiscally and operationally prudent techniques and devices to improve the safety of children in ambulances.

Molecular systematics of the North American chub genus Macrhybopsis (Teleostei: Cyprinidae).

The North American fish genus Macrhybopsis (Teleostei: Cyprinidae) as presently conceived comprises 12 species and occurs in much of interior eastern North America. Variation in the mitochondrial ND2 gene and the nuclear S7 intron 1 reveal conflicting gene-tree relationships for deeper nodes, which are assumed to represent past introgression and heterospecific mitochondrial fixation. The results support monophyly for the wide-ranging M. aestivalis complex with successive sister relationships to M. gelida, M. meeki, and M. storeriana. The current species-level taxonomy of Macrhybopsis is generally supported. Species status is supported for the morphologically distinct M. australis and M. tetranema, both of which are genetically introgressed by M. hyostoma. The results agree with previous suggestions that the wide-ranging M. hyostoma harbors cryptic species. Similar crypticity is indicated for the poorly sampled M. storeriana; a sample from the Pearl River shows 8% ND2 divergence from two Mississippi River populations. Within the M. aestivalis complex, there are only two examples of geographic overlap among mtDNA phylogroups. One involves co-occurrence of the highly divergent M. marconis and M. cf. hyostoma, and the other is the detection of the apparently anthropogenic occurrence of mitochondrial DNA from a Red River form, either M. cf. hyostoma or M. australis, in the Cimarron River of the Arkansas River basin.

Practice Patterns of Dentist Anesthesiologists in North America.

This study provides trends in the discipline of dental anesthesiology. A questionnaire-based survey was sent to 338 members of the American Society of Dentist Anesthesiologists to evaluate practice patterns. One focus of the study was modality of sedation/anesthesia used for dentistry in North America. Age, gender, years in practice, and geographic region of practice were also obtained. Data gathered from the returned questionnaires were entered into an Excel spreadsheet and then imported into JMP Statistical Discovery Software (v12.2 Pro) for descriptive analysis. A total of 112 surveys were completed electronically and 102 surveys were returned via post, for a total response rate of 63.3% ( N = 214). Data from this survey suggested a wide variation of therapeutic practices among dentist anesthesiologists in North America. Of the surveyed dentist anesthesiologists, 58.7% (SE = 4.2%) practice as mobile providers, 32.2% (SE = 3.1%) provide care in an academic environment, and 27.7% (SE = 2.8%) function as operator/anesthetists. The majority of anesthesia is provided for pediatric dentistry (47.0%, SE = 4.2%), oral and maxillofacial surgery (18.5%, SE = 3.9%), and special needs (16.7%, SE = 3.6%). Open-airway (58.7%, SE = 5.5%) sedation/anesthesia was the preferred modality of delivery, compared with the use of advanced airway (41.3%, SE = 4.6%). The demographics show diverse practice patterns of dentist anesthesiologists in multiple regions of the continent. Despite concerns regarding specialty recognition, reimbursement difficulties, and competition from alternative anesthesia providers, the overall perceptions of dentist anesthesiologists and the future of the field seem largely favorable.

Molecular systematics and historical biogeography of the Nocomis biguttatus species group (Teleostei: Cyprinidae): nuclear and mitochondrial introgression and a cryptic Ozark species.

The Nocomis biguttatus species group ranges widely across North America from the Red River in Oklahoma and Arkansas north to Minnesota and east-west from Wyoming to Ontario. The group includes three traditionally recognized allopatric species: the wide-ranging N. biguttatus and two geographically more restricted species, N. asper from the western Ozarks (Arkansas River system) and two disjunct locations in the Red River system, and N. effusus from the Green, Cumberland, and lower Tennessee rivers. Separate analyses of the mitochondrial cytb gene and two nuclear genes (S7 intron 1 and a portion of the gene for growth hormone, GH), each resolved a cryptic species previously treated as N. biguttatus from the southern Ozarks (White River). Relationships among the four species were unresolved because of conflicts between cytb and S7 and a lack of resolution for GH. A previously indicated N. biguttatus-N. effusus sister-relationship appears to reflect past hybridization and mtDNA capture by N. effusus. Nocomis biguttatus includes four primary cytb clades with unresolved inter-relationships. A Northern Ozarks-Great Plains-Upper Midwest Clade and an Ohio River-Eastern Great Lakes Clade presumably represent late Quaternary dispersal from glacial refugia in, respectively, the northern Ozarks and an unglaciated portion of the Ohio River system. Other clades include one from the Meramec River and a Black River-St. Francis River Clade. There was evidence in N. effusus for a phylogeographic break between the lower Tennessee River and the Green-Cumberland basins. Geographic structure is weak in N. asper, indicating relatively recent contact between now disjunct populations in the Arkansas and Red river basins. The Blue River population of N. asper appears to reflect late Pleistocene or Holocene hybridization and genetic swamping of a resident native population of N. biguttatus by an invading population of N. asper. This postulates past occurrence of N. biguttatus far south of its present range.

Red blood cell transfusion: impact of an education program and a clinical guideline on transfusion practice.

BACKGROUND: Red blood cell (RBC) transfusion guidelines have been developed by professional societies. These guidelines recommend a restrictive RBC transfusion practice for most clinical populations. Despite the consistency of guidelines and limited evidence for RBC transfusion efficacy, there is variability in RBC transfusion practice. METHODS: A program was initiated in a tertiary medical center to align RBC transfusion practice with best-practice RBC transfusion guidelines. The program included an educational program, followed after 6 months by RBC transfusion decision support that included the approval of a best-practice RBC transfusion guideline by the hospital medical board and an RBC transfusion order form that included the guideline recommendations. RBC transfusion practice was followed over an 18-month period and compared with transfusion practice over the prior 18 months. The primary outcome variables were adult inpatient RBC units transfused, RBC units per admission, and RBC units per 100 patient-days. RESULTS: The mean RBC units transfused decreased with initiation of each component of the program: from 923 ± 68 units to 852 ± 40 (P = 0.025) with education and further to 690 ± 52 (P < 0.0001) with the RBC transfusion decision support. Similarly, RBC transfusions per 100 patient-days fell from 10.56 ± 0.80 to 9.69 ± 0.49 (P = 0.02) and to 7.68 ± 0.63 (P = 0.0001) during the 3 time periods. CONCLUSION: An education program coupled with institutional adoption of a best-practice RBC transfusion guideline and RBC transfusion order set resulted in a reduction in total RBC units transfused.

The differential effect of NAT2 variant alleles permits refinement in phenotype inference and identifies a very slow acetylation genotype.

Indirect evidences suggest that acetylation phenotype categories are heterogeneous and that subcategories, related to specific NAT2 variant alleles might exist. We analyzed the in vivo acetylation phenotype and genotype in 504 north-American subjects of Caucasian origin. The analyses of the SNPs rs1801280 and rs1799930 allowed the discrimination of five categories with different acetylation status within the study population. These categories are related to the distinct effect of NAT2 alleles on the acetylation status in vivo and to the occurrence of a gene-dose effect. These five phenotype categories, from higher to lower acetylation capacity, correspond to the genotypes NAT2*4/*4, NAT2*4/*5 or *4/*6, NAT2*5/*5, NAT2*5/*6 and NAT2*6/*6 (p ≤ 0.001 for all comparisons). The NAT2*6/*6 genotype correspond to a phenotype category of very-slow acetylators. The refinement in phenotype prediction may help to identify risks associated to phenotype subcategories, and warrants the re-analysis of previous studies that may have overlooked phenotype subcategory-specific risks.

The certifying examination of the american board of surgery: the effect of improving communication and professional competency: twenty-year results.

PURPOSE: In 1985, a small research group identified variables affecting applicant success on the oral Certifying Examination (CE) of the American Board of Surgery (ABS). This led to the design of an oral examination course first taught in 1991. The success of and need for this program led to its continuation. The results from the first 10 years were presented at the 2001 Association of Program Directors in Surgery annual meeting.(1) We now report the outcomes for the course of the second 10 years as measured by success on the CE. METHODS: Thirty-six courses were held over 20 years. There were 57 invited faculty from 27 general surgery programs throughout the United States and Canada. The participant-to-faculty ratio ranged from 16:7 to 5:1 in the newer 3-day format (2007). Courses were offered at sites that replicated the actual examination setting. Each course included (1) pretest and posttest examinations, (2) analysis of case presentation skills, (3) measurement of communication apprehension, (4) 1:1 faculty feedback, (5) small-group practice sessions, (6) individual videotaping, (7) didactic review of specific behaviors on examinations, (8) a debrief session with two faculty members, and (9) a written evaluative summary that included an improvement strategy. RESULTS: There were 36 courses with 326 participants (30-54 years). Follow-up data are available for 225 participants. Trends were analyzed between 1991-2001 and 2002-2011. As resident performance on the CE increased in importance, applicant profiles changed from those who had previously failed (1991-2001) to residents identified by program directors as needing assistance (52%). Since 2002, most course participants (69%) who had failed the CE had completed at least 1 other review course. Participants reported more significant stressors (2002-2011) 9%, but communication apprehension remained the same. As a result, individual counseling for anger and family stressors was integrated into the course. The perception of knowledge deficits was associated with those who enrolled in fellowship training and delayed their examination. The recent groups exhibited more professionalism and articulation issues related to performance. Five surgeons (2002-2011) were asked not to return to the course because of severe knowledge deficiencies or ethical/behavioral issues based on faculty evaluations. Although complete follow-up of all participants was not possible (only 225/326), the success rate among those providing follow-up was 97% for those who followed their remediation plan, giving 218/326, a worse-case pass rate of 67%. CONCLUSION: Communication and professionalism deficits are still common in those struggling with the CE, Early identification of those at risk of failing by program directors who are documenting the competencies may promote earlier interventions and thus lead to success. This program continues to be effective at identifying behaviors that interfere with success on the CE of the ABS.

Functional genetic variants in the 3'-untranslated region of sulfotransferase isoform 1A1 (SULT1A1) and their effect on enzymatic activity.

Sulfotransferase isoform 1A1 (SULT1A1) is the most highly expressed hepatic sulfotransferase and is involved in the biotransformation of a wide variety of endo- and xenobiotics. A common single nucleotide polymorphism (SNP) in the coding region of SULT1A1, several proximal promoter SNPs, and copy number variation (CNV) are associated with altered enzymatic activity, but these variants do not fully account for the observed variation of SULT1A1 activity in human populations. In order to identify additional SNPs modulating SULT1A1 activity, we examined the 3'-untranslated region (UTR) of SULT1A1 in 97 liver samples. Direct sequencing revealed that two SNPs in the 3'-UTR (902A > G [rs6839] and 973C > T [rs1042157]) and one SNP in the 3'-flanking region (1307G > A [rs4788068]) were common. These SNPs are in absolute linkage disequilibrium with each other and in tight linkage with SULT1A1 1/2 (linkage coefficient D' 0.83) and are significantly associated with SULT1A1 messenger RNA (p = 0.001, 0.029, 0.021) and enzymatic activity (p = 0.022, 0.012, 0.027). We then examined the collective effects of 3'-UTR SNPs, SULT1A1 1/2, and CNV on SULT1A1 activity in 498 Caucasian and 127 African-American subjects by haplotype analysis. This analysis revealed that SULT1A1 1/2 does not contribute to the variation in SULT1A1 enzymatic activity when the 3'-UTR SNPs are included in the statistical model. Two major haplotypes (ACG and GTA) were significantly correlated with SULT1A1 activity, and when stratified by copy number, the SULT1A1 3'-UTR SNPs remain significantly associated with SULT1A1 enzymatic activity in Caucasians, but not in African-Americans. Subsequent functional characterization revealed that a microRNA, miR-631, regulates SULT1A1 expression in a genotype-specific manner.

Polymorphisms in inflammatory genes, plasma antioxidants, and prostate cancer risk.

BACKGROUND: Presence of xenotropic murine leukemia virus-related virus and chronic inflammation in prostate tumor suggests that inflammation plays a role in prostate cancer etiology. This study investigated whether variants in inflammatory genes act alone or interact with plasma antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas. METHODS: Cases (n = 193) were men, aged 40-80, diagnosed with prostate cancer in three major hospitals in 1998-2003, and controls (n = 197) were matched to cases by age, race, and county of residence. RESULTS: After adjustment for confounders, polymorphisms in COX-2 (rs689466) and IL-8 (rs4073) were not significantly associated with prostate cancer risk. However, apparent interactions were observed between these genetic variants and plasma antioxidants on the risk of this malignancy. The protective effect of the mutant allele of the COX-2 polymorphism was more pronounced among subjects with high plasma levels of beta-cryptoxanthin, lycopene, beta-carotene, or selenium (>or=median) [e.g., OR (95% CI): 0.37 (0.15, 0.86) (AG/GG vs. AA) for beta-cryptoxanthin]. Conversely, the promoting effect of the variant allele of the IL-8 polymorphism was more remarkable in subjects with low plasma levels of Lutein/zeaxanthin, beta-cryptoxanthin, and beta-carotene (

Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants.

OBJECTIVES: To investigate whether polymorphisms in genes involved in the repair of oxidative DNA damage, modulate, and/or interact with antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas. Accumulating evidence indicates that oxidative stress plays a role in prostate carcinogenesis. METHODS: Cases (n = 193) included men aged 40-80 years, diagnosed with prostate cancer in 3 major hospitals in 1998-2003, and controls (n = 197) were matched to cases by age, race, and county of residence. RESULTS: After adjustment for confounders, subjects who were heterozygous or homozygous for the variant allele of the hOGG1 Ser326Cys polymorphism appeared to experience a lower risk of prostate cancer than those who were homozygous for the wild-type allele (odds ratio [OR] (95% confidence interval [CI]): 0.72 (0.46-1.10)]. Conversely, a significant increased risk was observed for individuals who carried 1 or 2 copies of the variant allele of the XRCC1 Arg399Gln polymorphism, compared with those who only harbored the wild-type allele (OR [95% CI]: 1.56 [1.01-2.45]). The above-mentioned associations were generally more pronounced among subjects with low plasma carotenoids or alpha-tocopherol (

Physical activity, diet, and pancreatic cancer: a population-based, case-control study in Minnesota.

Although mounting evidence suggests that insulin resistance is involved in pancreatic carcinogenesis, few epidemiologic studies have comprehensively investigated the role of lifestyle factors influencing this metabolic disorder in the etiology of pancreatic cancer. We sought to examine this problem in a case-control study conducted in 1994-1998 in Minnesota. Cases (n = 186), aged 20 yr or older, were ascertained from all hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic; from the latter, only cases residing in the Upper Midwest of the United States were recruited. Controls (n = 554) were randomly selected from the general population and frequency matched to cases by age (within 5 yr) and sex. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. After adjustment for confounders, physical activity was associated with a reduced risk, but this protective effect was confined to light activity and moderate activity only (OR = 0.55, 95% CI = 0.30-0.97, P(trend) = 0.038 and OR = 0.51, 95% CI = 0.28-0.93, P(trend) = 0.07, for highest vs. lowest quartile, respectively). An increased risk was found for dietary intakes of energy and fat but was statistically significant for saturated and polyunsaturated fat only. Of note, no appreciable difference in the magnitude of the associations existed between saturated, monounsaturated, and polyunsaturated fat. Compared with individuals in the lowest quartile of fiber intake, the risk was approximately halved for those in the third (OR = 0.49, 95% CI = 0.26-0.94) and the highest quartile (OR = 0.52, 95% CI = 0.21-1.30). Our study lends support to the hypothesis that dietary and other lifestyle factors influencing insulin resistance modulate pancreatic cancer risk.

Phenotypic CYP2A6 variation and the risk of pancreatic cancer.

OBJECTIVE: Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme capable of activating several procarcinogens, including dietary and tobacco-specific nitrosamines, which have been linked to pancreatic cancer. Positive associations between high CYP2A6 activity and lung and colorectal cancers have been reported. This is the first investigation of CYP2A6 activity and pancreatic cancer. DESIGN: In this case-control study of cancer of the exocrine pancreas, phenotypic CYP2A6 activity was measured using a ratio of urinary caffeine metabolites. Demographic, smoking, dietary and medical information were obtained by questionnaire. CYP2A6 phenotype, which is not influenced by smoking status, was measured for 90 cases and 470 controls. RESULTS: When modeled as a continuous variable, and adjusted for age, sex, race, education, current smoking status and chronic pancreatitis, the odds ratio (OR) per one unit of the natural log of the CYP2A6 ratio was 1.52 (95% confidence interval, CI: 1.09-2.12). In an adjusted categorical analysis, subjects in the uppermost quartile (based on controls) of CYP2A6 activity, when compared to the lower three quartiles, carried an 80% greater risk of pancreatic cancer (OR=1.80; 95% CI: 1.07-3.02). CONCLUSIONS: High levels of CYP2A6 activity, as measured by a caffeine phenotyping assay, were positively associated with pancreatic cancer in this casecontrol study among a Midwestern U.S. population.

Association of demographic and treatment variables in long-term colon cancer survival.

The purpose of this study is to examine demographic and treatment variables because they relate to 5-year survival in colon cancer. The study design is analysis of 174 471 patients with colon and rectosigmoid cancer as reported to the American College of Surgeons National Cancer Data Base. Factors associated with a reduced risk of mortality included female gender (hazard ratio = 0.89; 95% confidence interval, 0.87-0.90), education status (hazard ratio = 0.87; 95% confidence interval, 0.85-0.89), increased number of lymph nodes resected (compared with <8, 8-12: hazard ratio = 0.90; 95% confidence interval, 0.89-0.92; >12: hazard ratio = 0.79; 95% confidence interval, 0.77-0.80), and addition of chemotherapy (hazard ratio = 0.69; 95% CI, 0.68-0.71). African American race (hazard ratio = 1.14; 95% confidence interval, 1.11-1.18) and increasing age correlated with an increased hazard risk (61-75 years: hazard ratio = 1.26; 95% confidence interval, 1.23-1.29; >or=76 years: hazard ratio = 2.15; 95% confidence interval, 2.09-2.21, compared with age <60 years). Survival in colon cancer is significantly impacted by patient's age, race, gender, and education status but not by income or area of residence.

The UGT2B17 gene deletion polymorphism and risk of prostate cancer. A case-control study in Caucasians.

BACKGROUND: UDP-glucuronosyltransferase (UGT) 2B17 is a phase II metabolizing enzyme that mediates the glucuronidation of C(19) steroids. A deletion polymorphism in the UGT2B17 gene is associated with a substantial reduction in glucuronidation activity in vitro. METHODS: We examined the association between the UGT2B17 deletion polymorphism and the risk of incident prostate cancer in a population-based study from central Arkansas that included 411 Caucasian cases and 397 Caucasian controls. We developed a novel high-throughput procedure that uses real-time PCR and allelic discrimination for genotyping analysis. RESULTS: The prevalence of the UGT2B17 deletion [(0/0)] was 12% in the controls, which was consistent with previous population estimates and with Hardy Weinberg equilibrium. There was no association between the UGT2B17 deletion polymorphism and prostate cancer risk in unconditional logistic regression analysis. Compared to the wild-type group (+/+), the adjusted odds ratio (OR) was 0.89 (95% CI=0.55-1.45) for the homozygous deletion (0/0), and the OR was 0.99 (95% CI=0.73-1.35) for the heterozygote group (+/0). CONCLUSION: These findings show that the UGT2B17 deletion polymorphism is not associated with prostate cancer risk in Caucasians.

Plasma carotenoids and prostate cancer: a population-based case-control study in Arkansas.

Carotenoids possess antioxidant properties and thus may protect against prostate cancer. Epidemiological studies of dietary carotenoids and this malignancy were inconsistent, partially due to dietary assessment error. In this study, we aimed to investigate the relation between plasma concentrations of carotenoids and the risk of prostate cancer in a population-based case-control study in Arkansas. Cases (n = 193) were men with prostate cancer diagnosed in 3 major hospitals, and controls (n = 197) were matched to cases by age, race, and county of residence. After adjustment for confounders, plasma levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin were inversely associated with prostate cancer risk. Subjects in the highest quartile of plasma lycopene (513.7 microg/l) had a 55% lower risk of prostate cancer than those in the lowest quartile (140.5 microg/l; P trend = 0.042). No apparent association was observed for plasma alpha-carotene and beta-carotene. Further adjustment for the other 4 carotenoids did not materially alter the risk estimates for plasma lycopene, lutein/zeaxanthin, and beta-cryptoxanthin but appeared to result in an elevated risk with high levels of plasma alpha-carotene and beta-carotene. The results of all analyses did not vary substantially by age, race, and smoking status. This study added to the emerging evidence that high circulating levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin are associated with a low risk of prostate cancer.

Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) mediates cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation in adenomatous polyposis coli (APC)min/+ mice. To assess the influence of thiazolidinediones (TZDs), which are PPAR ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted. PATIENTS AND METHODS: Data on male patients 40 years and older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained from the Veterans Integrated Services Network 16 (VISN 16) data warehouse. Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD, other antidiabetic agents, and insulin were identified. Cox regression with time-dependent covariates was used to estimate the association between TZD use and cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity, body mass index, use of insulin, and other oral antidiabetic agents). RESULTS: Of 87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and 1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal and prostate cancers did not reach statistical significance. CONCLUSION: TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.

Systematics of the subgenus Oligocephalus (Teleostei: Percidae: Etheostoma) with complete subgeneric sampling of the genus Etheostoma.

The genus Etheostoma is the most diverse clade of freshwater fishes in North America. While studies have been performed with complete sampling of a single subgenus, none have included representatives of all remaining subgenera. The subgenus Oligocephalus is the largest, consisting of 25-27 species in four species groups, and its monophyly has never been clearly demonstrated. The monophyly of this subgenus and its constituent groups was tested using parsimony and Bayesian analyses of ND2 (mtDNA) and the first intron of S7 (nDNA) with complete species sampling from Oligocephalus and complete subgeneric sampling from Etheostoma. Although the subgenus Oligocephalus was not recovered as a monophyletic group in any analyses, monophyletic E. whipplei, Southwestern Darter, and E. spectabile (in part) species groups were recovered in all analyses. All analyses agree that E. okaloosae and both subspecies of E. hopkinsi are not closely related to other members of the subgenus Oligocephalus. E. exile is, however, presenting the strongest evidence yet that recognition of the subgenus Boleichthys is unwarranted.

The urinary metabolite profile of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is predictive of colon DNA adducts after a low-dose exposure in humans.

Epidemiologic evidence indicates that exposure to heterocyclic amines in the diet is an important risk factor for the development of colon cancer. Well-done cooked meats contain significant levels of heterocyclic amines, which have been shown to cause cancer in laboratory animals. To better understand the mechanisms of heterocyclic amine bioactivation in humans, the most mass abundant heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was used to assess the relationship between PhIP metabolism and DNA adduct formation. Ten human volunteers where administered a dietary relevant dose of [(14)C]PhIP 48 to 72 hours before surgery to remove colon tumors. Urine was collected for 24 hours after dosing for metabolite analysis, and DNA was extracted from colon tissue and analyzed by accelerator mass spectrometry for DNA adducts. All 10 subjects were phenotyped for cytochrome P4501A2 (CYP1A2), N-acetyltransferase 2, and sulfotransferase 1A1 enzyme activity. Twelve PhIP metabolites were detected in the urine samples. The most abundant metabolite in all volunteers was N-hydroxy-PhIP-N(2)-glucuronide. Metabolite levels varied significantly between the volunteers. Interindividual differences in colon DNA adducts levels were observed between each individual. The data showed that individuals with a rapid CYP1A2 phenotype and high levels of urinary N-hydroxy-PhIP-N(2)-glucuronide had the lowest level of colon PhIP-DNA adducts. This suggests that glucuronidation plays a significant role in detoxifying N-hydroxy-PhIP. The levels of urinary N-hydroxy-PhIP-N(2)-glucuronide were negatively correlated to colon DNA adduct levels. Although it is difficult to make definite conclusions from a small data set, the results from this pilot study have encouraged further investigations using a much larger study group.

Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men.

PURPOSE: UDP-glucuronosyltransferases (UGT) are a family of enzymes that glucuronidate many endogenous chemicals, including androgens. This makes them more hydrophilic, alters biological activity, and facilitates their excretion. A deletion polymorphism in the UGT2B17 gene was recently described that was associated with a reduced rate of glucuronidation in vivo. The purpose of this study was to determine if the deletion polymorphism is associated with susceptibility to prostate cancer. MATERIALS AND METHODS: UGT2B17 expression was determined by reverse transcription-PCR of pathologically normal prostate tissues (n = 5). In a case-control study with 420 patients with incident primary prostate cancer (127 African Americans and 293 Caucasians) and 487 controls (120 African Americans and 367 Caucasians), the frequency of UGT2B17 deletion polymorphism in genomic DNA was compared between cases and controls with PCR analysis. RESULTS: UGT2B17 mRNA was detected only in individuals with at least one UGT2B17 allele. The frequency of the null genotype was present in 0.11 and 0.12 of Caucasian and African American controls, respectively. When all subjects were considered, a significant association was found between the UGT2B17 deletion polymorphism and prostate cancer risk [odds ratio (OR), 1.7; 95% confidence interval (95% CI), 1.2-2.6]. There was an increase in prostate cancer risk among individuals with UGT2B17 deletion polymorphism in Caucasians (OR, 1.9; 95% CI, 1.2-3.0) but not in African Americans (OR, 1.3; 95% CI, 0.6-2.7). CONCLUSIONS: These results suggest that the UGT2B17 enzyme may play a role in the metabolism of androgens in prostate tissue and that the UGT2B17 deletion polymorphism is associated with prostate cancer risk.

Discordance between N-acetyltransferase 2 phenotype and genotype in a population of Hmong subjects.

Polymorphisms of N-acetyltransferase 2 (NAT2) acetylation may influence drug toxicities and efficacy and are associated with a differential susceptibility to select cancers. Acetylation phenotype may have clinical implications. The purposes of this study were to determine the genetic basis of an apparent predominance of slow acetylation phenotype and to assess concordance with genotype in a population of Hmong residing in Minnesota. Urine and DNA obtained from unrelated Hmong 18 to 65 years of age were used to determine phenotype from caffeine metabolites, whereas direct nucleotide sequencing of the NAT2 coding region, followed by cloning, identified all known allelic variants. From 61 subjects (27 men, 30 +/- 11 years), analysis of 50 urine-DNA pairs identified 46 (92%) slow acetylators and 4 (8%) rapid acetylators by phenotype. Genotypic analysis inferred 5 (10%) slow acetylators and 45 (90%) rapid acetylators. There is 86% discordance between phenotype and genotype. A predominance of NAT2 slow acetylation phenotype in the Hmong is confirmed, and a significant discordance between NAT2 phenotype and genotype is identified. In this population, slow acetylation phenotype determined by a metabolic probe would not have been predicted by genotype alone. Environmental, genetic, or phenotypic anomalies that may contribute to this discordance should be considered and evaluated in future studies within this unique population.