Hallauer's Tusón: a decade of selection for tropical-to-temperate phenological adaptation in maize.

Crop species exhibit an astounding capacity for environmental adaptation, but genetic bottlenecks resulting from intense selection for adaptation and productivity can lead to a genetically vulnerable crop. Improving the genetic resiliency of temperate maize depends upon the use of tropical germplasm, which harbors a rich source of natural allelic diversity. Here, the adaptation process was studied in a tropical maize population subjected to 10 recurrent generations of directional selection for early flowering in a single temperate environment in Iowa, USA. We evaluated the response to this selection across a geographical range spanning from 43.05° (WI) to 18.00° (PR) latitude. The capacity for an all-tropical maize population to become adapted to a temperate environment was revealed in a marked fashion: on average, families from generation 10 flowered 20 days earlier than families in generation 0, with a nine-day separation between the latest generation 10 family and the earliest generation 0 family. Results suggest that adaptation was primarily due to selection on genetic main effects tailored to temperature-dependent plasticity in flowering time. Genotype-by-environment interactions represented a relatively small component of the phenotypic variation in flowering time, but were sufficient to produce a signature of localized adaptation that radiated latitudinally, in partial association with daylength and temperature, from the original location of selection. Furthermore, the original population exhibited a maladaptive syndrome including excessive ear and plant heights along with later flowering; this was reduced in frequency by selection for flowering time.

Transient hyperglycaemia in a prediabetic dog treated with prednisone and cyclosporin A.

A dog with immune-mediated haemolytic anaemia developed transient hyperglycaemia and glucosuria requiring insulin therapy in association with prednisone and cyclosporin A therapy. Following short-term therapy with insulin and cyclosporin A, the dog remained on prednisone therapy but required no further insulin therapy for 12 weeks, at which time the dog became permanently diabetic. We hypothesise that prednisone and cyclosporin A contributed to insulin resistance in a prediabetic dog with suboptimal endogenous insulin concentration and that the degree of insulin resistance decreased when cyclosporin A therapy was discontinued.

The practices and attitudes of primary care nurse practitioners and physician assistants with respect to colorectal cancer screening.

OBJECTIVES: Although nurse practitioners and physician assistants form a large and growing portion of the primary care workforce, little is known about their colorectal cancer screening practices. The aim of this study was to assess the colorectal cancer screening practices, training, and attitudes of nurse practitioners and physician assistants practicing primary care medicine. METHODS: All nurse practitioners (827) and physician assistants (1178) licensed by the Medical Board of the State of North Carolina were surveyed by mail. Both groups were further divided into primary care versus non-primary care by self-described roles. Self-reported practices, training, and attitudes with respect to colorectal cancer screening were elicited. RESULTS: Response rates were 71.4% and 61.2%, for nurse practitioners and physician assistants respectively. A total of 51.3% of nurse practitioners and 50.3% of physician assistants described themselves as adult primary care providers. No primary care nurse practitioners and only 3.8% of primary care physician assistants performed screening flexible sigmoidoscopy. However, 76% of primary care physician assistants and 69% of primary care nurse practitioners reported recommending screening flexible sigmoidoscopy. A total of 95% primary care physician assistants and 92% of primary care nurse practitioners reported performing fecal occult blood testing. Only 9.4% of physician assistants and 2.8% of nurse practitioners received any formal instruction in flexible sigmoidoscopy while in their training. Additionally, 41.4% of primary care physician assistants and 27.7% of primary care nurse practitioners reported that they would be interested in obtaining formal training in flexible sigmoidoscopy. CONCLUSIONS: Physician assistants and nurse practitioners are motivated, willing and underutilized groups with respect to CRC screening. Efforts to increase education and training of these professionals may improve the availability of CRC screening modalities.

Emergency contraception knowledge and prescribing practices: a comparison of primary care residents at a teaching hospital.

STUDY OBJECTIVE: To determine knowledge, opinion, and experience concerning emergency postcoital contraception in primary care physicians who are in training. DESIGN: Cross-sectional survey using a questionnaire survey distributed to primary care specialty housestaff. SETTING: Questionnaire surveys were distributed to all active primary care housestaff in training and Obstetrics and Gynecology attendings at the University of Kentucky. PARTICIPANTS: The study surveyed all primary care specialty housestaff. Specialties included family practice (FP), internal medicine (IM), pediatrics (PD), and obstetrics and gynecology (OG). The attending faculty in Obstetrics and Gynecology (OGA) were also surveyed as a comparison group. MAIN OUTCOME MEASURES: Study variables were compared between specialty of training, year of training, and abortion opinion. ANOVA or Student's t tests were used, with statistical significance defined as P <.05. Each questionnaire was scored 0 to 9 based on knowledge and utilization questions. Overall response rate was 48%, 90 out of 189 surveyed. Response rates per specialty are as follows: FP = 51%, IM = 37%, PD = 48%, OG = 65%, and OGA = 69%. RESULTS: The average score on the survey was significantly different based on specialty of training (P value <. 0001). Scores were not significantly different based on year of training. However, the average attending OG's score was significantly higher than for all the housestaff (P value <.0001). CONCLUSION: Knowledge and utilization of postcoital contraception is dependent on specialty. Unfortunately, this knowledge does not appear to increase with year of training, suggesting that there is a lack of education during the years of training.

Crohn's disease: does race matter? The Mid-Atlantic Crohn's Disease Study Group.

OBJECTIVE: The severity of Crohn's disease (CD) has been reported to be greater in blacks than in whites. This possible disparity may be due, in part, to differences between these groups in health care utilization and accessibility. To explore these issues, we conducted a multicenter survey of patients with CD. METHODS: One-hundred and forty-five blacks with CD, recruited from four teaching hospitals and five private practices, and identified by medical record review or ICD-9 code, were enrolled and matched to 407 whites with CD (by age, gender, and practice type [teaching vs. private practice setting]). Participants were interviewed regarding medical history, health status, personal health care practices during the preceding 5 yr, and beliefs regarding health care in the general population. RESULTS: Blacks and whites were similar with respect to age of CD onset, lag in time to diagnosis, and number of gastrointestinal (GI)-related hospitalizations and surgeries. Medication usage patterns were also similar in the two groups. Quality of life, measured by SF-36, was lower in all categories for blacks, compared with whites. Blacks were more likely to have had to stop work (p<0.01) and have lost more work days (p<0.01) than were whites. Whites were more likely to have health insurance and be able to identify a regular provider than were blacks. Blacks were more likely to report the following: receiving Medicaid; difficulty affording health care; delaying appointments due to financial concerns; difficulty traveling to their provider's office; and experiencing unreasonable delays at their provider's office. After adjusting for potential confounding variables, we found no differences between the groups, except for the number of days of work lost because of CD. CONCLUSIONS: These data suggest that black and white patients have similar reported disease presentations and course, and contrast with prior reports suggesting a more severe disease course among black patients. Although the disease itself appears similar, there were numerous reported differences between the races in health care utilization practices and in disease impact upon daily activities. We suggest that apparent disparities in CD according to race are actually due to social and economic factors, and not to the disease itself.

Rectal mucosal proliferation, dietary factors, and the risk of colorectal adenomas.

Colorectal cancer arises from a series of precursor stages, the so called adenoma-carcinoma sequence. Increased rectal mucosal proliferation may be an early step in this sequence. Because dietary factors are implicated in the etiology of colorectal cancer, one might predict that diet would also be associated with proliferation. We conducted this study to examine the association of diet with rectal mucosal proliferation. Rectal mucosal proliferation was measured in endoscopic biopsy specimens by proliferating cell nuclear antigen (PCNA) immunohistochemistry and whole crypt mitotic counts (WCMCs). Diet was evaluated using a validated quantitative food frequency questionnaire. The correlation between PCNA labeling index (LI) and WCMCs was determined using Kendall's tau, a nonparametric measure of correlation. Logistic regression was used to examine the effect of proliferation on adenoma status, controlling for confounders. The relationship between proliferation and dietary and demographic factors was examined using linear regression. There were 308 patients who had one or both measures of proliferation. There was no significant correlation between PCNA LI and WCMCs (Kendall's tau = 0.04; P = 0.35). Neither measure of proliferation was predictive of adenoma status, even after adjusting for potential confounders. Body mass index and calories per day were significant predictors of WCMC (P = 0.01 and P = 0.03, respectively). PCNA labeling index was not associated with any dietary variables, although its association with dietary fat nearly reached statistical significance (P = 0.09). The association between proliferation and diet were generally inconsistent. There appears to be no simple relationship between colorectal cancer risk factors, colorectal adenomas, and these two measures of rectal mucosal proliferation. We need simpler, more reliable intermediate markers for use in etiological and intervention studies.

XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of Frasier syndrome.

STUDY OBJECTIVE: To report a case of XY gonadal dysgenesis in an adolescent with renal failure and to review the literature on this association. METHODS: In this case report from the Tertiary Care University Medical Center, a 16-year-old female with chronic renal failure presenting with primary amenorrhea was studied. Interventions included laparotomy with bilateral gonadectomy and hormone replacement therapy. MAIN OUTCOME MEASURES: Karyotype, gonadal histology. RESULTS: Diagnosis of gonadal dysgenesis. Presence of a gonadoblastoma. CONCLUSIONS: Gonadal dysgenesis should be considered in any female adolescent with renal disease presenting with pubertal delay or primary amenorrhea.

Aspirin and nonsteroidal anti-inflammatory agents and risk for colorectal adenomas.

BACKGROUND & AIMS: Aspirin and nonsteroidal anti-inflammatory drugs have been reported to protect against the development of colorectal cancer. Because adenomas are precursors to most colorectal cancers, the aim of this study was to examine the relationship of these medications to the risk for colorectal adenomas in a colonoscopy-based case-control study. METHODS: Study participants were drawn from patients who underwent colonoscopy at the University of North Carolina Hospitals. Medication use was assessed by telephone using a comprehensive list of prescription and nonprescription drugs as well as questions about dietary and lifestyle factors that might be relevant for adenoma development. RESULTS: There were 210 patients with adenomas and 169 adenoma-free controls. After adjusting for potential confounders, regular users were half as likely to currently have adenomas compared with nonusers (adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.92). Regular users who stopped medication at least 1 year before colonoscopy were still protected (adjusted odds ratio, 0.59; 95% confidence interval, 0.21-1.67), although small numbers make this conclusion tentative. The protective effects of aspirin and the nonaspirin nonsteroidal anti-inflammatory drugs were similar. CONCLUSIONS: The results suggest that aspirin and nonsteroidal anti-inflammatory drugs cause early disruption of the adenoma-carcinoma sequence. The challenge for the future will be to learn more about dose, duration, and mechanism of action.

In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia.

BACKGROUND & AIMS: To investigate whether mitogen-activated protein kinase (MAPK) cascades might play a role in the progression of colon cancer, c-Jun N-terminal kinase (JNK) and extracellular signal regulating kinase (ERK) activity during colonic tumorigenesis were examined. METHODS: The 1,2-dimethylhydrazine (DMH)-induced colon carcinoma model was used to study the activation of these kinases during intestinal carcinogenesis. Male Sprague-Dawley rats were injected with DMH for 24 weeks. Normal-appearing intestinal mucosa from control and treated animals and DMH-induced intestinal tumors were assayed for JNK and ERK activity using solid phase in vitro kinase assays. Tumors were typed for mutations in the K-ras gene. RESULTS: There was little or no difference in JNK and ERK activity in hyperproliferative mucosa from DMH-treated animals compared with normal mucosa from control animals. However, in 16 colonic neoplasms, an average of 23-fold and 29-fold increases in JNK and ERK activities were observed, respectively, over control levels. In addition, activating protein-1 binding was strongly induced in the colonic tumors. Activation did not correlate with the presence of mutations in K-ras. CONCLUSIONS: Both the JNK and ERK MAPKs are highly activated during late progression of colorectal carcinoma. This change is dependent on the tumorigenic state rather than changes in proliferation.

Sperm interaction with fallopian tube apical membrane enhances sperm motility and delays capacitation.

OBJECTIVE: To understand the effect of sperm contact with the apical plasma membrane of tubal epithelial cells on sperm motility, velocity, and capacitation. DESIGN: Prospective, controlled in vitro study. SETTING: University medical center. PATIENT(S): Women of reproductive age undergoing hysterectomy for benign gynecologic indications and normozoospermic donors of proved fertility. MAIN OUTCOME MEASURE(S): Sperm motility as measured manually, velocity as measured by computer-assisted sperm motility analysis, and capacitation status as measured by the chlortetracycline fluorescence assay. RESULT(S): Sperm incubated with apical membrane vesicles had a significantly higher motility at 12 (87.4% +/- 3.4% versus 69.2% +/- 4.8% [mean +/- SEM]), 24 (85.2% +/- 3.1% versus 60.5% +/- 7.2%) and 48 hours (78.9% +/- 5.3% versus 42.4% +/- 11.3%) compared with control (sperm incubated with human tubal fluid media in the absence of apical membrane vesicles) (n = 4). Progressive velocity was significantly higher at 12 (78.2 +/- 1.4 versus 61.7 +/- 16.1 microns/s) and 24 (66.2 +/- 3.9 versus 34.4 +/- 9.8 microns/s) hours (n = 4). Incubation with apical membrane vesicles significantly slowed the transition from uncapacitated to capacitated chlortetracycline fluorescence pattern (n = 5). CONCLUSION(S): Contact with the apical plasma membrane of tubal epithelial cells enhances sperm motility and delays sperm capacitation in vitro.

Intestinal effects of sulfate in drinking water on normal human subjects.

Uncontrolled observations implicate sulfate in drinking water at concentrations exceeding 500-700 mg/liter as a cause of diarrhea, but controlled studies have not been reported. We conducted a controlled study in normal adults to determine the effect of various drinking water sodium sulfate concentrations on bowel function. Ten healthy subjects were given a constant diet and fluid intake. Fluid consisted of 36 ml/kg/day of drinking water of various known sulfate concentrations and 500 ml of other fluid. In a dose-ranging study, four subjects received drinking water with sulfate concentrations of 0, 400, 600, 800, 1000, and 1200 mg/liters for six consecutive two-day periods. In a single-dose study, six other subjects received water with sulfate concentrations of 0 and 1200 mg/liter for two consecutive six-day periods. Stool mass, frequency, and consistency and mouth-to-anus appearance time of colored markers were measured. In the dose-ranging study, the only significant linear trend was decreasing mouth-to-anus appearance time with increasing sulfate concentrations. In the single-dose study, 1200 mg/liter sulfate caused a significant but clinically mild increase in mean stool mass per six-day pool from 621 g to 922 g (P = 0.03). When all 10 subjects were used to compare effects of 0 mg/liter and 1200 mg/liter sulfate, significant differences in stool consistency (P = 0.02) and transit time (P = 0.03) were observed. None of the subjects reported diarrhea or passed more than three stools per day. In 10 normal adult subjects, sulfate in drinking water at a concentration of 1200 mg/liter, which is higher than reported to occur in US municipal water sources, caused a measurable but clinically insignificant increase in stool mass and decrease in stool consistency and appearance time, but no change in stool frequency and no complaint of diarrhea.

Effective treatment of severe menstrual migraine headaches with gonadotropin-releasing hormone agonist and "add-back" therapy.

OBJECTIVE: To determine the efficacy of treating women with severe menstrual migraine headaches with GnRH agonist (GnRH-a) therapy, alone and combined with continuous estrogen-progestin "add-back." DESIGN: Nonrandomized, prospective treatment study. SETTING: Outpatient clinic in a university medical center. PATIENT(S): Five women who had repetitive, severe, migraine headaches limited to the perimenstrual period were selected carefully. INTERVENTION(S): After 2 months of basal evaluation, all subjects received GnRH-a (leuprolide acetate depot formulation, 3.75 mg IM, monthly) for 10 months. Beginning with the 5th month, "add-back" therapy (the addition of transdermal E2, 0.1 mg daily, and oral medroxyprogesterone acetate, 2.5 mg daily) was initiated. MAIN OUTCOME MEASURE(S): Patients rated headache severity from 0 (absent) to 3 (severe) each day; these were combined each month to obtain a cumulative score for that month. In addition, patients were asked their overall assessment of the treatments. RESULT(S): The mean headache scores for the GnRH-a treatment months (4.0 +/- 1.5, mean +/- SEM) and for the GnRH-a and "add-back" treatment months (3.1 +/- 0.7) were each significantly lower than those of the control months (15.3 +/- 2.4). The patients uniformly found both treatments to be well tolerated and near-curative for their condition. CONCLUSION(S): Gonadotropin-releasing hormone agonist administration, alone or with "add-back" therapy, is a very effective treatment for carefully selected patients with severe, perimenstrual migraine headaches.

Plasma selenium levels and the risk of colorectal adenomas.

Previous research has suggested that selenium may protect against the development of colorectal neoplasia. We examined the potential chemopreventive properties of selenium against colorectal adenomas while controlling for a number of dietary and life-style factors. We conducted a cross-sectional study among patients referred for colonoscopy to University of North Carolina Hospitals. Cases had one or more pathologically confirmed adenomas, and noncases had none. Plasma selenium levels were determined using graphite furnace atomic absorption spectrometry with Zeeman background correction and platform technique. Odds ratios were calculated using logistic regression analysis adjusting for potential confounders. The mean plasma selenium concentrations for cases (n = 37) and noncases (n = 36) were 107 and 120 micrograms/l, respectively (p = 0.06). Those in the fourth quartile of plasma selenium level had 0.24 times the risk (95% confidence interval = 0.06-1.04) for colorectal adenomas of those in the first quartile. The adjusted odds ratio for colorectal adenomas was 0.58 (95% confidence interval = 0.31-1.08) for a 30 microgram/l increase in plasma selenium level. Lower plasma selenium levels were associated with multiple adenomas but not with adenoma size or location. These data support a protective effect of selenium against colorectal adenomas after adjustment for possible confounders. Selenium might be a potentially useful chemopreventive agent for colorectal neoplasia.

Micronutrients and the risk of colorectal adenomas.

Recent studies suggest that micronutrients, especially folate, calcium, iron, and antioxidant vitamins, affect the risk of colorectal neoplasia. The objective of this case-control study was to examine the association between these micronutrients and the risk of colorectal adenomas. The study was based on 236 cases with adenomatous polyps or cancer and 409 controls, all colonoscopy patients at University of North Carolina Hospitals between July 1988 and March 1991. After colonoscopy, subjects were interviewed using a semi-quantitative food frequency questionnaire, and average daily nutrient intakes were calculated. Sex-specific odds ratios relative to the lowest quartile of intake for each micronutrient were determined using unconditional logistic regression while adjusting for a number of potential confounders. In women, folate, iron, and vitamin C were inversely related to the risk of adenomas. Folate appeared to be most protective, with women in the highest quartile only 40% as likely to develop adenomas compared with women in the lowest (odds ratio = 0.39, 95% confidence interval 0.15-1.01). In men, greater vitamin E and calcium intakes were associated with reduced risk of adenomas, with vitamin E showing the strongest inverse association. Men in the highest vitamin E quartile had a risk of 0.35 (95% confidence interval 0.14-0.92) relative to those in the lowest. These study results support previous research findings that selected micronutrients protect against colorectal neoplasia.

Regulation of granulosa cell-derived ovarian metalloproteinase inhibitor(s) by prolactin.

Increased prolactin concentrations are known to inhibit the ovarian proteolytic enzyme cascade associated with follicular rupture. It is not known whether there is also an effect of prolactin on endogenous proteinase inhibitors such as the tissue inhibitors of metalloproteinases (TIMPs). We sought to study the effect of prolactin on ovarian metalloproteinase inhibitors in cultured rat granulosa cells. Granulosa cells were cultured for 24 h with prolactin (0-1000 ng ml-1) in the absence or presence of LH. Metalloproteinase inhibitor activity in the conditioned culture media was measured by a colorimetric assay. Prolactin at 1000 ng ml-1 increased inhibitor activity by 2.86 +/- 0.63 times. Expression of mRNA encoding TIMP-1 measured by Northern analysis increased by 2.34 +/- 0.34 times with 100 ng prolactin ml-1 and by 2.43 +/- 0.42 times with 1000 ng prolactin ml-1 compared with control cultures (no LH, no prolactin). In the presence of LH, expression of mRNA encoding TIMP-1 and inhibitor activity increased by 2.60 +/- 0.6 and 4.60 +/- 0.54 times, respectively. However, no further change in mRNA expression or inhibitor activity was apparent with the addition of prolactin to LH-treated cultures. Prolactin had no effect on expression of mRNA encoding TIMP-3 in the absence or presence of LH, although LH stimulated a 1.7-fold increase in mRNA encoding TIMP-3 compared with controls. Addition of prolactin had no effect on media concentrations of oestradiol or progesterone. These data demonstrate that metalloproteinase inhibitor activity increases with increasing doses of prolactin; however, when LH was added, this effect was no longer seen. With an increase in metalloproteinase inhibitor activity, tissue metalloproteinase action could be decreased, providing a possible explanation for the local inhibition on pre- and peri-ovulatory pathways by hyperprolactinaemia.

Comparison of rectal mucosal proliferation measured by proliferating cell nuclear antigen (PCNA) immunohistochemistry and whole crypt dissection.

Rectal mucosal proliferation has been promoted as an intermediate marker for risk of colorectal neoplasia. Proliferating cell nuclear antigen (PCNA) immunohistochemistry has become a standard method to measure cell proliferation. Whole-crypt dissection may provide a technically simpler method for determining proliferation within an entire crypt. We conducted a study to assess the reliability (reproducibility) of whole-crypt dissection in 10 subjects. Reliability of whole-crypt dissection with the subject as the unit of observation was excellent. The intraclass correlation coefficient for subjects was 0.93. Biopsy-to-biopsy reliability was lower (r=0.86) and crypt-to-crypt reliability lower still (r = 0.35). There was poor correlation between measures of proliferation index using the two techniques (Kendall's tau = 0.13; P = 0.08). Compartment analysis based on the percentage of the total number of labeled cells appearing in each crypt quartile also did not demonstrate a significant correlation between the two measures. We conclude that PCNA labeling index and whole-crypt mitotic count are not comparable measures of rectal mucosal proliferation.

Reproducibility and variability of the rectal mucosal proliferation index using proliferating cell nuclear antigen immunohistochemistry.

Rectal mucosal proliferation has been shown to be increased in patients with neoplastic lesions of the large bowel and may serve as a marker of risk for colorectal malignancy. We conducted analyses to determine reliability and components of variability that might suggest optimal analysis strategies for studies of proliferation. Endoscopic pinch biopsies were obtained from 17 adult patients, labeled using proliferating cell nuclear antigen, scored using strict rules, and then rescored. Labeling index, defined as the proportion of labeled cells in a crypt, was calculated for each crypt, biopsy, subject, and group. There was excellent reproducibility. The technician was able to select previously scored crypts 95% of the time. The overall labeling index was identical on repeat. There was considerable variability in labeling index among crypts from a single biopsy and between biopsies of a single subject. Variance component estimates suggested that 20% of the variability of labeling index was due to subject, 30% due to the biopsy within a subject, and 50% due to crypts within a biopsy. There were substantial gains in statistical power by scoring two biopsies rather than one. There was less gain from further increases in biopsy number. There was little statistical advantage for counting more than 8 crypts/biopsy. Demonstrating a decrease of 25% in the mean labeling index with 90% power could require more than 100 subjects/group. We conclude that proliferating cell nuclear antigen is an extremely reproducible method to determine proliferation index. There is considerable variability among subjects, biopsies, and crypts.(ABSTRACT TRUNCATED AT 250 WORDS)