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Biomedical subjects

A Kendall

Publications and source records attributed to A Kendall.

At least 19 recordsLinked to original sources

Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer. PATIENTS AND METHODS: Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women. RESULTS: Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women. CONCLUSIONS: The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.

Aromatase Inhibitors↗

Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer.

BACKGROUND: Currently available treatment for hormone refractory prostate cancer is limited in efficacy and associated with significant toxicity. This phase II study was performed to assess the efficacy of the oral fluoropyrimidine capecitabine in advanced prostate cancer. PATIENTS AND METHODS: Patients who had a rising prostate-specific antigen (PSA) despite androgen withdrawal, but who remained free from cancer-related symptoms. In total, 14 patients received oral capecitabine 1250 mg/m2 twice daily for two weeks of a three-week cycle. Tumour response was assessed using serum PSA measurement at 3-weekly intervals and, where present, imaging of soft tissue metastases. RESULTS: One of 14 patients experienced a partial response as assessed by both PSA and imaging of liver metastases. In seven other patients (50%), treatment decreased the rate of PSA rise. The duration of PSA stabilisation was generally short, but in 5/14 patients (36%) was sustained beyond 18 weeks, and in one patient to 24 weeks. Toxicity was significant but manageable, the most common adverse events being nausea, mucositis and hand-foot syndrome, each occurring in 50% of patients. Other common side effects were diarrhoea and lymphopenia. All toxicities were grade 1 or 2, except for grade 3 hand-foot syndrome occurring in one patient, and no dose reduction was required because of toxicity. CONCLUSION: Capecitabine has limited activity as a single agent in prostate cancer, but appears to modulate tumour biology. Considering the added convenience of oral administration, these results support further evaluation of combinations containing capecitabine in hormone-refractory prostate cancer.

Administration, Oral↗

Signet ring cell carcinoma in the prostate.

Metastases to the prostate gland are rare and often found in the context of widespread metastatic disease. We report an unusual case of primary gastric signet ring cell adenocarcinoma (SRCC) diagnosed over 1 year after treatment for metastatic disease in the prostate.

Aged↗

Evaluation of psychosocial measures for understanding weight-related behaviors in pregnant women.

The greatest weight gain for US. women occurs during the childbearing years of 25 to 34, and many obese women attribute their adult weight gain to childbearing. Few studies have examined psychosocial influences on women's behaviors during pregnancy, in part because of the lack of valid and reliable measures of psychosocial constructs relevant to pregnant women. Based on existing theory and an in-depth interview study, the psychosocial constructs of locus of control, self-efficacy, body image, feelings about motherhood, and career orientation were identified. Scales for each construct were constructed by drawing items from existing validated scales and writing items based on the in-depth interviews; their content validity assessed using factor analysis with oblique rotation and their reliability using Cronbach's alpha. Construct validity was assessed by examining the associations between scale scores and preexisting conditions of participants. Data for evaluating the scales came from a study of 622 pregnant women in a rural health care system who completed questionnaires and whose medical records were audited. Cronbach's alpha of the scales ranged from 0.73 to 0.89. Scale scores were strongly associated with lifestyle behaviors, body weight, and demographic characteristics of the participants. The analysis provides evidence of the validity of measures of psychosocial factors related to health behaviors of pregnant women. These measures should be useful in studying weight-related behaviors in pregnant women.

Adolescent↗

A CBF5 mutation that disrupts nucleolar localization of early tRNA biosynthesis in yeast also suppresses tRNA gene-mediated transcriptional silencing.

In the budding yeast, Saccharomyces cerevisiae, actively transcribed tRNA genes can negatively regulate adjacent RNA polymerase II (pol II)-transcribed promoters. This tRNA gene-mediated silencing is independent of the orientation of the tRNA gene and does not require direct, steric interference with the binding of either upstream pol II factors or the pol II holoenzyme. A mutant was isolated in which this form of silencing is suppressed. The responsible point mutation affects expression of the Cbf5 protein, a small nucleolar ribonucleoprotein protein required for correct processing of rRNA. Because some early steps in the S. cerevisiae pre-tRNA biosynthetic pathway are nucleolar, we examined whether the CBF5 mutation might affect this localization. Nucleoli were slightly fragmented, and the pre-tRNAs went from their normal, mostly nucleolar location to being dispersed in the nucleoplasm. A possible mechanism for tRNA gene-mediated silencing is suggested in which subnuclear localization of tRNA genes antagonizes transcription of nearby genes by pol II.

Cell Nucleolus↗

Novel nonpeptidic inhibitors of peptide deformylase.

A novel series of nonpeptidic compounds structurally related to the known anticholesteremic thyropropic acid were found to inhibit Escherichia coli peptide deformylase (PDF), with IC50 values in the low-micromolar range. Kinetic analysis of [4-(4-hydroxyphenoxy)-3,5-diiodophenyl]acetic acid reveals competitive inhibition, with a Ki value of 0.66 +/- 0.007 microM. A structure-activity relationship study demonstrates that the carboxylate is required for activity, while the distal phenolic function can be methylated without significant effect. Either decreasing the number of iodine atoms on the molecule to one or increasing the number of iodine atoms to four results in the loss of an order of magnitude in potency. These compounds are the first nonpeptidic inhibitors disclosed and represent a template from which better inhibitors might be designed.

Amidohydrolases↗

Nucleolar localization of early tRNA processing.

There is little information as to the location of early tRNA biosynthesis. Using fluorescent in situ hybridization in the budding yeast, Saccharomyces cerevisiae, examples of nuclear pre-tRNAs are shown to reside primarily in the nucleoli. We also probed the RNA subunit of RNase P. The majority of the signal from RNase P probes was nucleolar, with less intense signals in the nucleoplasm. These results demonstrate that a major portion of the tRNA processing pathway is compartmentalized in nucleoli with rRNA synthesis and ribosomal assembly. The spatial juxtaposition suggests the possibility of direct coordination between tRNA and ribosome biosynthesis.

Base Sequence↗

Potent antimitotic and cell growth inhibitory properties of substituted chalcones.

A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line. (E)-3-(3"-Hydroxy-4"-methoxyphenyl)-2-methyl-1-(3',4',5'- trimethoxyphenyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active. A relationship between the conformation and cytotoxicity of the chalcones is discussed.

Antineoplastic Agents↗

Hunger and food insecurity in the elderly: its nature and measurement.

To better understand the nature of food insecurity in the elderly and to improve its measurement, in-depth interviews were conducted with 41 urban Black and rural White elderly in 35 households, followed by telephone administration of commonly used measures of food insecurity in 24 of these elderly. Elderly food insecurity appears to follow a progression of severity, beginning with compromised diet quality, followed by food anxiety, socially unacceptable meals, use of emergency food strategies, and finally actual hunger. The five quantitative measures tested were compared to each elderly person's food insecurity status based on the in-depth interview. All measures had reasonable specificity, and good sensitivity for those experiencing severe food insecurity. However, the Cornell-Radimer, Community Childhood Hunger Identification Project (CCHIP) and Nutrition Screening Initiative (NSI) measures appeared more sensitive than the USDA food sufficiency or Urban Institute measures in correctly identifying those in the lesser stages of food insecurity.

Aged↗

Questionnaire-based measures are valid for the identification of rural households with hunger and food insecurity.

This study assessed the validity of questionnaire-based measures for the identification of rural households with hunger and food insecurity. Data used were from a 1993 survey of 193 households with women and children living at home in a rural county. Two interviews provided data on demographics, factors contributing to food insecurity, coping strategies, fruit and vegetable consumption, disordered eating behaviors, height, weight, dietary recall and household food-stores inventory. This information was used to develop a definitive criterion measure for hunger and food insecurity to compare with hunger and food insecurity items from Radimer/Cornell, the Community Childhood Hunger Identification Project (CCHIP) and the Third National Health and Nutrition Examination Survey (NHANES III). The Radimer/Cornell and CCHIP questionnaire-based measures had good specificity (i.e., percentage of truly food secure correctly classified; 63-71%) and excellent sensitivity (i.e., percentage of truly food insecure correctly classified; 84-89%) when compared with the criterion measure. Estimates of the prevalence of household food insecurity from the criterion, Radimer/Cornell and CCHIP measures were almost identical. The overall agreement of the Radimer/Cornell and CCHIP measures was very good. These measures can be validly used to screen for hunger and food insecurity among rural households similar to those studied and to target subpopulations for food programs. The NHANES III item alone had excellent specificity but poor sensitivity, and underestimated prevalence.

Adaptation, Psychological↗

Relationship of hunger and food insecurity to food availability and consumption.

OBJECTIVE: To describe the relationship of new measures of hunger and food insecurity to household food supplies and individual food and nutrient intake. DESIGN AND SETTING: A questionnaire containing the Radimer/Cornell hunger and food insecurity items and questions on eating patterns and the frequency of fruit and vegetable consumption was administered to subjects during a personal interview in their homes. A 24-hour diet recall and a household food inventory were conducted at the initial interview and at a follow-up visit. SUBJECTS: Participants were 193 women drawn from a random sample of 308 women who had completed a previous health census in a rural New York State county. Subjects' ages ranged from 15 to 40 years. All had children living at home and less than 16 years of education. STATISTICAL ANALYSES: Regression analysis was used to test for linear trends across food insecurity groups for the household food inventory scores and for the frequency of consumption of fruits and vegetables. t Tests were used to assess differences between the food secure and food insecure groups for nutrient and food group means. A chi 2 test for trend was used to examine differences in the distribution of nutrient and fruit and vegetable intake between the food secure and food insecure groups. RESULTS: A significant decrease in the frequency of consumption of fruits and vegetables and the amount of food in the household and a significant increase in scores indicative of disordered eating patterns were associated with a worsening of food insecurity status. Potassium and fiber intake and fruit consumption differed significantly between the food secure and food insecure groups. The percentage of respondents consuming less than the Recommended Dietary Allowance for vitamin C and fewer than five fruits and vegetables per day was significantly greater among food insecure respondents than food secure respondents. APPLICATIONS/CONCLUSIONS: The quantity of food available in households and consumption of fruits and vegetables decreased with increasingly severe problems with food insecurity and hunger. In this rural population, the Radimer/ Cornell measures were useful in identifying households experiencing food insecurity and providing information about the nature of the food supply and the dietary intake problems experienced by food insecure households and persons, suggesting that these measures may be useful on community surveys designed to examine food insecurity issues.

Adolescent↗

Validation of the Radimer/Cornell measures of hunger and food insecurity.

Hunger and food insecurity have been identified as core indicators of an individual's nutritional state that should be assessed in nutrition surveillance activities. Such an assessment requires a valid measure of these phenomena. This paper describes further work on the construction of measures of hunger and food insecurity based on the Radimer/Cornell items and provides an assessment of their validity. A random sample survey of 193 households with women and children living at home was conducted in 1993 in a rural county in New York State. A questionnaire containing the Radimer/Cornell hunger and food insecurity items, information about demographic characteristics, frequency of fruit and vegetable consumption, and household food supplies was administered to subjects. Measures were constructed that identified households experiencing household- and individual-level food insecurity and households with hungry children. The construct and criterion-related validity of the measures was assessed. In relation to criterion-related validity, as food insecurity worsened, there was a significant and progressive increase in the percentage of subjects participating in food programs and having low income, education and employment and a significant decline in average household food availability and fruit and vegetable consumption. These results support the validity of the Radimer/Cornell measures and illustrate their ability to differentiate among groups of households experiencing increasingly severe food insecurity and hunger.

Adolescent↗

Stress, anxiety, depression, and physical illness in college students.

The interrelationships among measures of stress, anxiety, depression, and physical illness in a proportional sample of college undergraduates (N = 184) were examined. Significant correlations were found in the stress-illness, anxiety-illness, depression-illness, and anxiety-depression relationships. Partial correlations demonstrated that the stress-illness relationship remained significant, though lowered, when first anxiety and then depression were held constant. In the second phase of the research the indices of stress, anxiety, depression, and illness were predicted to vary by both year in school and gender within this sample. Significant differences in reported stress and anxiety by year in school and in reported illness incidence by gender were found. Possible ties between these results and research on coping, social support, and gender roles are discussed.

Analysis of Variance↗

Phenotypic changes in T-cyt-transformed potato plants are consistent with enhanced sensitivity of specific cell types to normal regulation by root-derived cytokinin.

From over forty independently isolated potato lines transformed with wild-type and promoter-mutated T-cyt genes, a number of lines were selected for examination of phenotypic changes in growth and development for plants grown in soil in a controlled environment. The three lines chosen for most detailed examination showed a wide spectrum of phenotypic changes. In comparisons with control potato cv. Désirée, the plants of one line had a two- to three-fold increase in biomass production during early vegetative growth, advanced senescence and a shortened plant life-span. Another line showed abnormal cellulytic senescence. In two lines there were increases in tuber numbers and more skewed tuber size distributions which correlated with reduced shoot apical dominance and shortened dormancy of the stored tubers. None of the lines showed altered timing of onset of tuberization or flowering, although tuberization was consistently delayed when expressed as a function of increasing total plant weight. A hypothesis is proposed to explain the diverse phenotypes which postulates that (1) T-cyt transformation causes enhanced sensitivity to cytokinins in specific types of shoot cells which are already targets for regulation by normal root-derived cytokinins; (2) two distinct types of shoot target cells are present, one in shoot meristems and one in leaves; (3) the two types can acquire enhanced sensitivity, either separately or in combination depending on the particular T-cyt transformation event. The scope for using the transformed plants in subsequent physiological, biochemical and molecular studies, aimed at examining the molecular basis of the model or selected consequences of T-cyt transformation in altering regulation of potato plant growth and development, is discussed. The attention is drawn to the possible involvement at the subcellular level of sucrose phosphate synthase in mediating the phenotypic effects caused by T-cyt transformation.

Adaptation, Physiological↗