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Biomedical subjects

S Curry

Publications and source records attributed to S Curry.

At least 19 recordsLinked to original sources

Crystallization and preliminary X-ray analysis of three serotypes of foot-and-mouth disease virus.

Foot-and-mouth disease viruses from serotypes O, A and C have been crystallized. The particular strains studied include O1K, A10(61), A22 Iraq 24/64, A24 Cruzeiro and C-S8c1. In addition, crystals have been grown of G67, a monoclonal antibody neutralization escape mutant derived from O1K, and of virus R100, recovered after the establishment of a persistent infection in baby hamster kidney cells with C-S8c1. Empty particles, capsids which lack the RNA genome, have also been crystallized for subtypes A22 Iraq 24/64 and A10(61). In almost all cases, crystals suitable for high resolution structure determination were obtained from (NH4)2SO4 or mixtures of polyethylene glycol and NH4Cl.

Aphthovirus

Multi-level analysis in epidemiologic research on health behaviors and outcomes.

Individual-level health behaviors and outcomes have multi-level determinants (individual and environmental). Multi-level analysis seeks to explain individual outcomes in terms of both individual and environmental or aggregate variables. Ecologic fallacy (improper inference about individual-level associations based on associations measured only at the aggregate level) can result from confusion about the level of inference that is of ultimate interest. The perspective of multi-level analysis acknowledges the importance of both individual and environmental variables in determining health behaviors and outcomes at the level of the indivisible unit--the individual. The authors review concepts and methods of multi-level analysis and their application to epidemiologic research on health behavior and health outcomes.

Chronic Disease

Correlates of maintenance of a low-fat diet among women in the Women's Health Trial.

BACKGROUND: The Women's Health Trial (WHT) was a feasibility study for a randomized controlled trial designed to test the hypothesis that a reduction in dietary fat reduces breast cancer incidence among women age 45 to 69. Between 1984 and 1988, 2,064 women participated in its two phases. METHODS: A follow-up study of 525 women who were randomized to receive the WHT dietary intervention program was conducted to assess maintenance of the diet 1 year on average after the trial ended. Among 448 participants, the mean percentage of energy from fat as measured by a food frequency questionnaire was 40.0% at baseline, 26.3% at the end of the trial, and 27.7% at follow-up. Based on 408 women with complete data, a recursive model was estimated, describing the influence of baseline characteristics of the women on attendance at intervention program sessions, adherence to the diet during the trial, and long-term maintenance of the diet after the trial ended. The effects of women's experiences during the trial on adherence and long-term maintenance were investigated as well. RESULTS: Attendance at the educational sessions was strongly related to adherence to the diet during the trial (P less than 0.001), and adherence was the most important predictor of long-term maintenance (P less than 0.001). The percentage of energy from dietary fat at baseline was an important correlate of both adherence (P less than 0.001) and long-term maintenance (P less than 0.001). College-educated women were more likely to adhere to the diet during the trial (P less than 0.001). Feelings of deprivation adversely affected long-term maintenance (P less than 0.01), primarily through their effect on adherence during the trial (P = 0.01). Costliness of the diet in time and money negatively influenced long-term maintenance (P less than 0.05). Development of a distaste for fat encouraged adherence (P = 0.06). CONCLUSIONS: The low-fat dietary pattern established during the WHT was maintained for as long as 20 months after the trial ended. A recursive model was useful in analyzing the process and correlates of long-term maintenance of dietary behavior change. Both predisposing variables and women's experiences while on a low-fat diet were associated with long-term maintenance. The results suggest that feelings of deprivation should be avoided, perhaps by use of low-fat substitutes, by those attempting to lower their dietary fat and that more research is needed on the development of a distaste for fat among individuals who adopt low-fat diets.

Aged

Mandibular remodeling measured on cephalograms. 1. Osseous changes relative to superimposition on metallic implants.

We report the results of a study aimed at quantifying remodeling of mandibular surfaces in a sample of growing children who represent those usually treated by orthodontists in the mixed and early adult dentition. The sample, 31 patients with metallic implants of the Björk-type, was monitored at annual intervals between 8 1/2 and 15 1/2 years of age. (Maxillary remodeling changes for the sample have been reported earlier.) The present article reports findings concerning changes at condyle, gonion, menton, pogonion, and point B as identified on lateral cephalograms. Data are reported in the Frankfort plane frame of reference with the cephalograms from different time points superimposed on the metallic implants. Mean displacement at condyle was larger than that at any other landmark and was similar in magnitude and direction to the observations of Björk when the difference in orientation of the vertical axis in the two studies is taken into account. The mean displacement of gonion was in an upward and backward direction at an angle of approximately 45 degrees to the Frankfort plane. Mean displacements at menton and pogonion were in a downward and backward direction but were very small. Mean displacement at point B was somewhat greater than that of menton and gonion, oriented in an upward and backward direction. Individual variation for most of the parameters measured was sufficiently large to warrant the inference that caution should be used when mean values are applied to the analysis of individual cases.

Adolescent

Mandibular remodeling measured on cephalograms: 2. A comparison of information from implant and anatomic best-fit superimpositions.

This study quantifies the differences in the perceived pattern of mandibular remodeling when two different methods are used to superimpose roentgenographic images of the mandible. Lateral cephalograms for a group of subjects with metallic implants of the Björk type were superimposed twice; first on the metallic implants and then independently on mandibular anatomic structures according to a common "best fit" rule. In this article, we compare the between-superimposition differences in the perceived displacements of condyle, gonion, menton, pogonion, and Point B. Mean differences between the two superimpositional techniques were smaller than had been anticipated. For the 7-year time interval between 8.5 and 15.5 years, the largest mean differences between methods were 2.70 mm in the horizontal direction at condyle, 1.90 mm in the vertical direction at condyle, and 1.52 mm in the vertical direction at gonion. None of the other between-superimposition differences had a mean value in excess of 1 mm. The individual case variability between the two methods was, however, quite considerable, a finding that we believe has bearing on the confidence that can be placed in individual case analyses in clinical orthodontics. A preliminary attempt has been made to represent and discuss the magnitude of this problem.

Adolescent

Long-term maintenance of a low-fat diet: durability of fat-related dietary habits in the Women's Health Trial.

The Women's Health Trial (WHT) was a feasibility study for a randomized trial of a low-fat diet for the prevention of breast cancer. One year after the WHT was terminated, a random sample of 894 participants who had been active in the WHT for an average of 16 months (range = 5 to 37) completed questionnaires about their dietary habits (a 21-item instrument that measures five dimensions of low-fat dietary habits) and food intake (a food frequency questionnaire). Women who participated in the intervention program maintained most of the low-fat dietary habits adopted during the study: mean total fat intake increased from 37.8 g to 41.0 g and scales describing substitution of specially manufactured low-fat foods and modification of meats to be lower in fat increased only slightly (by 0.11 and 0.14, respectively, on a scale of 1 = always to 4 = never). Scales describing avoiding meat and avoiding fats as a flavoring increased by 0.23 and 0.22, respectively, which suggests some recidivism. Women in the control group lowered their dietary fat intake from 65.0 to 57.5 g, but all differences in fat intake and fat-related dietary habits scales between women in the control and intervention groups remained highly statistically significant. In multiple regression models, all five low-fat dietary habits scales were independently associated with percentage of energy from fat, but the strongest association was for avoiding fats as flavorings. These results suggest that substitutions of specially manufactured low-fat foods are easily adopted and maintained dietary changes, but that maintenance of new habits related to avoiding fats as flavorings and avoiding meat will require long-term reinforcement strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Mapping the polarity profiles of general anesthetic target sites using n-alkane-(alpha, omega)-diols.

The effects of the homologous series of n-alkane-(alpha, omega)-diols have been studied on the inhibition of the purified firefly luciferase enzyme from Photinus pyralis, the inhibition of the purified bacterial luciferase enzyme from Vibrio harveyi, and the induction of general anesthesia in Xenopus laevis tadpoles. All but one of the diols tested were found to be reversible general anesthetics. The diols inhibited firefly luciferase by competing with its normal substrate firefly luciferin, and they inhibited bacterial luciferase by competing with the substrate n-decanal. For all but the smallest agent (1,4-butanediol), only a single diol molecule was found to be involved in the inhibition of the enzymes. Inhibition constants Ki were determined for the enzymes, and general anesthetic EC50 concentrations were determined for tadpoles. These data were then used in conjunction with previously determined n-alkane and n-alcohol data to calculate, as a function of chain length, the incremental standard Gibbs free energies delta (delta G0) for adding apolar -CH2- groups and for converting apolar terminal -CH3 groups to polar -CH2OH groups. The resulting plots of delta (delta G0) versus chain length gave a consistent mapping of the polarity profiles of the anesthetic-binding pockets. They clearly reveal the existence of two substantial and distinct polar regions in the anesthetic-binding pocket of firefly luciferase but only one such region for bacterial luciferase and for the unknown target sites underlying general anesthesia. The polarities and geometric properties of these different binding sites for straight-chain anesthetics are discussed in terms of simple models.

Anesthetics

Sampling elderly in the community: a comparison of commercial telemarketing lists and random digit dialing techniques for assessing health behaviors and health status.

A study of health behaviors in four communities in the western United States in 1988 provided the opportunity to compare two methods of sampling elderly respondents for a telephone interview. The Polk telemarketing lists were used to identify 1,407 respondents aged 65 years and older in four communities, where 253 respondents in the same age group were also identified by the method of random digit dialing. Individuals identified from the Polk lists received a letter prior to the initial telephone contact. The overall response rate was 49.3% for random digit dialing and 57.3% for the Polk lists. On the average, the identification of one elderly respondent using the Polk lists required about 20-25% as much interviewer time per subject identified as was required by the random digit dialing method. The elderly identified by the Polk lists were significantly older than those identified by random digit dialing, and the proportions of the Polk sample who were married, white, or had an income of greater than $10,000 were slightly higher than those of the random digit dialing sample. Among 40 variables measuring various health behaviors, indicators of health status, and participation in health-related programs and classes, only three differed significantly between the two samples. The authors conclude that sampling from commercial telemarketing lists was an efficient method of identifying elderly respondents and that in these four communities, the estimates of health behaviors and health status were comparable with those obtained by random digit dialing techniques.

Aged

Community-level comparisons between the grocery store environment and individual dietary practices.

BACKGROUND: This article examines the relationship at the community level between individual dietary practice and the grocery store environment. METHODS: Individual dietary practice was measured in 12 communities using a telephone survey to obtain self-reported diet. A protocol was developed to measure two aspects of the grocery store environment in these same 12 communities: the relative availability of healthful (low-fat and high-fiber) products, and the amount of health-education information provided. Comparisons were made between individual and store-level measures at two levels of geographic aggregation: community (typically a county) and zip code within community (n = 34). RESULTS: We found positive and statistically significant correlations at both the community and the zip code level between the availability of healthful products in stores and the reported healthfulness of individual diets. Positive correlations were also found between measures of the amount of health-education material provided by stores and the healthfulness of individual diets, but these correlations did not reach statistical significance. CONCLUSIONS: The results provide support for including measures of the grocery store environment as part of a community-level assessment of dietary behavior.

Adult

Probing the molecular dimensions of general anaesthetic target sites in tadpoles (Xenopus laevis) and model systems using cycloalcohols.

1. The series of cycloalcohols C6, C7, C8 and C10 have been used to probe the molecular dimensions of a variety of general anaesthetic target sites. 2. The general anaesthetic EC50 concentrations of the cycloalcohols were determined for tadpoles (Xenopus laevis). All of the cycloalcohols tested were found to be potent general anaesthetics (on average EC50/Csat = 0.03). 3. The effects of the cycloalcohols on highly purified luciferase enzymes from fireflies (Photinus pyralis) and bacteria (Vibrio harveyi) were also investigated. Both enzymes were inhibited competitively, with the cycloalcohols competing with firefly luciferin for binding to the firefly enzyme and with n-decanal for binding to the bacterial enzyme. 4. The binding site on the firefly enzyme could accommodate two molecules of cycloalcohols C6 and C7 but only a single molecule of the larger cycloalcohols (C8 and C10), implying a volume of the binding site of about 250 cm3 mol-1. In contrast, the binding site on the bacterial luciferase could bind only a single cycloalcohol molecule between C6 and C10. 5. While all of the cycloalcohols were potent inhibitors of the firefly luciferase enzyme (on average EC50/Csat = 0.015), they were very weak inhibitors of the bacterial luciferase enzyme (on average EC50/Csat = 0.12). Since both enzymes bind long-chain aliphatic n-alcohols tightly, the differing affinities of the cycloalcohols for the two enzymes is probably a consequence of geometrical factors. 6. The cycloalcohols produced very small effects on lipid bilayers. At EC50 concentrations which produce general anaesthesia, lipid bilayer phase transitions were shifted, on average, by only 0.43 degrees C. 7. We conclude that the general anaesthetic effects of the cycloalcohols can most economically be explained by assuming that the cycloalcohols act at protein binding sites in the central nervous system. These target sites would have binding properties similar to those of the anaesthetic-binding site on firefly luciferase, but their average volume would be somewhat smaller than 250 cm3 mol -1.

Alcohols

Effects of general anesthetics on the bacterial luciferase enzyme from Vibrio harveyi: an anesthetic target site with differential sensitivity.

The effects of a diverse range of 36 general anesthetics and anesthetic-like compounds on a highly purified preparation of the bacterial luciferase enzyme from Vibrio harveyi have been investigated. Under conditions where the flavin site was saturated, almost all of the anesthetics inhibited the peak enzyme activity and slowed the rate of decay. However, a small number of the more polar agents only inhibited at high concentrations, while stimulating activity at lower concentrations. The inhibition was found to be competitive in nature, with the anesthetics acting by competing for the binding of the aldehyde substrate n-decanal. The anesthetic binding site on the enzyme could accommodate only a single molecule of a large anesthetic but more than one molecule of a small anesthetic, consistent with the site having circumscribed dimensions. The homologous series of n-alcohols and n-alkanes exhibited cutoffs in inhibitory potency, but these cutoffs occurred at very different chain lengths (about C10 for the n-alkanes and C15 for the n-alcohols), mimicking similar cutoffs observed for general anesthetic potencies in animals. Binding constants determined from peak height measurements showed that the inhibitor binding site was predominantly hydrophobic (with a mean delta delta G CH2 of -5.0 kJ/mol), but fluctuations in the binding constants with chain length revealed regions in the binding site with polar characteristics. Binding constants to an intermediate form of the enzyme (intermediate II) were also determined, and these confirmed the principal features of the binding site deduced from the peak height measurements. The long-chain compounds, however, bound considerably tighter to the intermediate II form of the enzyme, and this was shown to account for the biphasic decay kinetics that were observed with these compounds. Overall, there was poor agreement between the EC50 concentrations for inhibiting the luciferase enzyme from V. harveyi and those which induce general anesthesia in animals, with bulky compounds being much less potent, and moderately long chain alcohols being much more potent, as luciferase inhibitors than as general anesthetics.

Alcohols

Intrinsic and extrinsic motivation for smoking cessation.

An intrinsic-extrinsic model of motivation for smoking cessation was evaluated with 2 samples (ns = 1.217 and 151) of smokers who requested self-help materials for smoking cessation. Exploratory and confirmatory principal components analysis on a 36-item Reasons for Quitting (RFQ) scale supported the intrinsic-extrinsic motivation distinction. A 4-factor model, with 2 intrinsic dimensions (concerns about health and desire for self-control) and 2 extrinsic dimensions (immediate reinforcement and social influence), was defined by 20 of the 36 RFQ items. The 20-item measure demonstrated moderate to high levels of internal consistency and convergent and discriminant validity. Logistic regression analyses indicated that smokers with higher levels of intrinsic relative to extrinsic motivation were more likely to achieve abstinence from smoking.

Adult

Evaluating community-based nutrition programs: assessing the reliability of a survey of grocery store product displays.

A pilot test of a survey of grocery store product displays was conducted to measure the amount of health-education information provided and the proportion of the display devoted to "healthier" products. Inter-rater reliability ranged between 0.73 and 0.78 for the healthiness indices and between 0.30 and 0.67 for the health education measures. Test-retest reliability ranged from 0.44 to 1.0.

Food Labeling

Smoking.

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Forecasting

Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study.

A randomized clinical trial was conducted in women with stage III ovarian carcinoma (less than or equal to 1 cm residual lesions), using cyclophosphamide plus cisplatin (CP) with or without doxorubicin. There were 349 evaluable patients, of whom 176 received CP while 173 patients received CP plus doxorubicin (CAP). Hematologic toxicity was almost identical. There was no significant difference in progression-free interval (PFI) (median, 22.7 months and 24.6 months), frequency of negative second-look laparotomy (30.2% and 32.8%), or survival (median, 31.2 months and 38.9 months) between CP and CAP, respectively. Thus, doxorubicin in the dose schedule employed does not improve combination chemotherapy of optimal stage III ovarian carcinoma. Several other findings, independent of treatment arm, were of interest. There was a significant difference in PFI and survival by residual disease category (yes v no) and by grade of differentiation (1 v 2 + 3). In multivariate analysis, age, residual disease at entry, cell type (clear cell carcinoma), and time from surgery to initiation of chemotherapy were significant predictors of survival. There was no difference in outcome comparing those who refused second-look with those who had a second-look.

Adult

Single-dose actinomycin-D treatment for nonmetastatic gestational trophoblastic disease. A prospective phase II trial of the Gynecologic Oncology Group.

The Gynecologic Oncology Group (GOG) conducted a prospective trial of single-dose Actinomycin-D (ACT-D) given intravenously (IV) at 1.25 mg/m2 every 2 weeks to patients with nonmetastatic gestational trophoblastic disease (NMGTD) in order to determine the efficacy of pulse scheduling and the frequency and severity of associated toxicity. Of 31 evaluable patients, 29 (94%) achieved remission after receiving a median of four courses of therapy. Two patients who failed to respond to pulse therapy were subsequently cured by alternative treatment. There were 93 toxic events in 133 cycles of therapy. Ninety-two percent of adverse effects were graded as mild or moderate, and 8% were graded as severe. No life-threatening toxicity occurred. Although single-dose ACT-D efficacy and toxicity is comparable to conventional therapy for NMGTD, the advantages of easier administration, greater patient convenience, and improved cost-effectiveness make it superior to other alternatives. On this basis it is recommended as the treatment of choice for NMGTD.

Adolescent

Phase II trial of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) combination chemotherapy in advanced ovarian carcinoma.

A monthly four-drug regimen of cyclophosphamide, adriamycin, and cis-dichlorodiammineplatinum(II), each given iv of Day 1, and hexamethylmelamine, given orally on Days 1--14 (CHAP), was administered to 39 women with advanced epithelial ovarian carcinoma who had previously failed alkylating agent therapy. Of 35 evaluable patients with a measurable disease parameter, seven (20%) achieved a clinical complete response and ten (29%) achieved a clinical partial response. The median duration of complete response is greater than 9 months and the median duration of partial response is 4 months. Ninety percent of the patients required dose adjustments because of profound leukopenia, thrombocytopenia, or gastrointestinal intolerance. CHAP is an active but toxic regimen in the management of advanced ovarian cancer. The toxicity encountered reflected the intensity of the drug schedule as well as the combined influences of advanced stage of disease, poor nutritional and performance status, and prior therapy. The efficacy of this CHAP regimen warrants a controlled trial compared to other active drug programs.

Alkylating Agents