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Biomedical subjects

M Hetherington

Publications and source records attributed to M Hetherington.

17 recordsLinked to original sources
PubMed1998

Cytotoxic activities of Mannich bases of chalcones and related compounds.

Various Mannich bases of chalcones and related compounds displayed significant cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of human tumor cell lines. The most promising lead molecule was 21 that had the highest activity toward L1210 and human tumor cells. In addition, 21 exerted preferential toxicity to human tumor lines compared to transformed human T-lymphocytes. Other compounds of interest were 38, with a huge differential in cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared. In general, the Mannich bases were more cytotoxic than the corresponding chalcones toward L1210 but not P388 cells. A ClusCor analysis of the data obtained from the in vitro human tumor screen revealed that the mode of action of certain groups of compounds was similar. For some groups of compounds, cytotoxicity was correlated with the sigma, pi, or molar refractivity constants in the aryl ring attached to the olefinic group. In addition, the IC50 values in all three screens correlated with the redox potentials of a number of Mannich bases. X-ray crystallography and molecular modeling of representative compounds revealed various structural features which were considered to contribute to cytotoxicity. While a representative compound 15 was stable and unreactive toward glutathione (GSH) in buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be one mechanism by which cytotoxicity was exerted in vitro. Representative compounds were shown to be nonmutagenic in an intrachromosomal recombination assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant and neurotoxic properties. Thus Mannich bases of chalcones represent a new group of cytotoxic agents of which 21 in particular serves as an useful prototypic molecule.

Animals↗
PubMed1998

Reasons for initiation and cessation of eating in obese men and women and the affective consequences of eating in everyday situations.

Reasons for the initiation and termination of eating were investigated in 78 female and 36 male obese subjects following a weight control programme. Self-monitoring diaries were completed during a 24-h period, in which subjects selected the main reason for starting and stopping an eating episode. Additionally, subjects recorded mood before and after eating using visual analogue scales. Hunger was chosen as a reason to start eating in only 20% of cases. Environmental cues such as mealtime were selected as the main reason for the initiation of the majority of eating episodes. In contrast, self-assessments such as "I felt I had eaten enough" was the main reason for terminating eating (39.4%). Gender differences in the reasons for initiating eating revealed a greater tendency for men to initiate eating for environmental reasons than women, whereas the opposite was found for the termination of eating, with women more likely to stop eating for environmental reasons than men. Changes in affect during eating revealed a significant decline in negative emotions such as tension and tiredness, and in the heavier subjects a trend for increased happiness was observed following eating. As hunger was less commonly reported as a reason to start eating than external reasons, treatment strategies for the obese might benefit by targeting individual reasons for meal initiation.

Affective Symptoms↗
PubMed1997

Relative effects of carbohydrates and protein on satiety -- a review of methodology.

There is some evidence that the effects of carbohydrates and protein may differ with respect to satiety. This may depend in part on the different methods of preparing these nutrients for administration. Additional factors such as timing, different delays, differential metabolism and expectations of ingested foods may contribute to different outcomes of experiments investigating the satiating effects of macronutrients. Here, studies of the relative satiating effects of carbohydrates and protein are discussed followed by a methodological discussion of the reviewed studies. Finally, suggestions for methodological improvements are given which should allow future studies to investigate more clearly the mechanisms underlying satiety.

Animals↗
PubMed1996

(Aryloxy)aryl semicarbazones and related compounds: a novel class of anticonvulsant agents possessing high activity in the maximal electroshock screen.

A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated for anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and neurotoxicity (NT) screens. The results indicated that greater protection was obtained in the MES test than the scPTZ screen. Quantitation of approximately one-third of the compounds revealed an average protection index (PI, i.e. TD50/ED50) of approximately 9. After oral administration to rats, a number of compounds displayed significant potencies in the MES screen (ED50 of 1-5 mg/kg) accompanied by very high protection indices. In fact over half the compounds had PI figures of greater than 100, and two were in excess of 300. The compounds were essentially inactive in the scPTZ and NT screens after oral administration to rats. Various compounds displayed greater potencies and PI figures in the mouse intraperitoneal and rat oral screens than three reference clinically used drugs. The data generated supported a binding site hypothesis. Quantitative structure-activity relationships indicated a number of physicochemical parameters which contributed to activity in the MES screen. X-ray crystallography of five compounds suggested the importance of certain interatomic distances and bond angles for activity in the mouse and rat MES screens.

Animals↗
PubMed1996

Thyroid function in bulimia nervosa.

Basal thyroid-stimulating hormone (TSH) and thyroid hormone levels were evaluated in 18 women with bulimia nervosa during a period of active binging and vomiting and again after 7 weeks of abstinence from these behaviors and compared to measures in 27 control women. In 10 of the patients and 11 of the controls, the TSH nocturnal surge was calculated from hourly TSH measurements obtained in the afternoon from 1500 to 1900 h and in the night from 2300 to 0400 h. During the binging phase of the illness patients had lower total triiodothyronine (T3) values than controls (p < .001). After 7 weeks without binge eating or purging, patients had lower T3, total thyroxine (T4), free triiodothyronine, free thyroxine (FT4), reverse triiodothyronine and thyroid-binding globulin (TBG) values compared to controls (p < .01) and significant reductions in T3, T4, FT4 and TBG compared to themselves in the active phase of the illness (p < .02). The reduction in thyroid hormone levels was not due to a reduction in the nocturnal thyrotropin surge, since surge values did not differ between normals and patients at either phase of the illness. Bulimics in the binging phase of the illness showed a positive correlation between caloric intake and TSH values (p < .01), suggesting that food binging may stimulate thyroid activity. In sum, these results show a substantial reduction in thyroid hormone levels after 7 weeks of abstinence from binging and vomiting behaviors.

Adult↗
PubMed1995

Debriefing the family: is research an intervention?

The primary focus of this article is to examine the general assumption that families are left largely unchanged by their participation in research, and to question whether family research can have unintended positive or negative effects on participants. The present article reports feedback from families participating in the Nonshared Environment and Adolescent Development project, a longitudinal study of family process and adolescent development. Families differed in their perceptions about whether the research experience was positive, detrimental, or inconsequential. This feedback underscores the researcher's ethical responsibility to detect and remove deleterious effects of participation. Suggestions are made for providing adequate debriefing to subjects and for using debriefing as a research tool to study the interaction between researcher and families.

Adolescent↗
PubMed1993

Heart rate/stroke volume relationship during upright exercise in long-term diabetics.

The changes in stroke volume (SV) during upright exercise were studied in 20 insulin-dependent diabetics (IDDM) and 20 age- and sex-matched controls. None of the diabetics had any cardiovascular symptoms. In addition, tests of autonomic function were conducted in the diabetics, assessing changes in heart rate (HR) during deep breathing and the Valsalva maneuver. During exercise the SV in the controls gradually increased and then remained essentially unchanged until maximum HR was achieved. Seven of the diabetics failed to sustain an initial increase in SV (fall > 15%), eight showed a "delayed" increase in SV, and the remaining five demonstrated an increasing SV over the range from rest to peak exercise. Abnormal autonomic function results were found during deep breathing (four diabetics) and the Valsalva maneuver (four diabetics). Findings indicate that cardiac function could be abnormal in IDDM without evidence of autonomic dysfunction. This abnormality could be due to a specific cardiomyopathy.

Adult↗
PubMed1989

The time course of sensory-specific satiety.

The time course of the changes in hedonic response following ingestion of three different foods was investigated. Normal weight, non-dieting female subjects rated the pleasantness of the appearance, smell, texture and taste of nine foods and then consumed as much as they wanted of cheese on cracker, tomato soup or orange jello. After this first course, subjects re-rated the pleasantness of the foods at 2, 20, 40 and 60 min. Following the 60 min rating, subjects were offered a second course of cheese on cracker or chocolate bar. For all sensory variables measured and for all foods consumed, the greatest decline in pleasantness occurred for the eaten food 2 min after consumption. For the food rate as most palatable (cheese on cracker) there was some recovery of pleasantness of the texture and taste over the hour. Intake in the second course was similar regardless of whether the food offered was different or the same as the food consumed in the first course. Since changes in the pleasantness of the foods occurred rapidly for all sensory variables studied and since the magnitude of these changes did not increase over time, it is concluded that the development of sensory-specific satiety is related primarily to the sensory stimulation accompanying ingestion as opposed to the postabsorptive effects of consuming these foods.

Adolescent↗
PubMed1988

Sensory stimulation and energy density in the development of satiety.

To determine the contribution of sensory stimulation to the changing hedonic response to foods, the effects of consuming very low-calorie and higher calorie versions of soup and jello on the subjective pleasantness of foods were compared. Subjects were 24 normal weight females with low dietary restraint. Half the subjects were given test meals of low- and high-calorie tomato soup and half were given low- and high-calorie orange jello. They rated the pleasantness of the appearance, smell, texture and taste of nine sample foods as well as hunger and stomach fullness before and 2, 20, 40 and 60 min after consumption of the test meal. After the 60 min rating subjects were offered as much as they wanted to eat of a second course of cheese on crackers. Despite differences in the energy density of the test meals, there were no significant differences in the weights of food eaten in either the first or second course and no significant compensation in the second course for the energy differences of the first course. No differential effects of the caloric manipulation were observed in terms of hunger or fullness or in the development, time course and magnitude of sensory-specific satiety. That very low-calorie foods can produce sensory-specific satiety indicates that the sensory properties of foods are important for the changing hedonic response to foods as they are consumed.

Adolescent↗
PubMed1988

The specificity of satiety: the influence of foods of different macronutrient content on the development of satiety.

The effects of consuming equicaloric preloads with different macronutrient contents on the development of satiety were investigated. Ten normal-weight, nondieting women fasted overnight and then rated hunger, fullness, and food preferences, and the pleasantness of the taste of food samples before and after five different preloads. The greatest changes in the pleasantness of the taste of the food occurred for the eaten food relative to the uneaten food. Macronutrient content of the preloads did not significantly influence the magnitude of these changes or the pleasantness of foods with similar nutrient contents. Therefore, no evidence of nutrient-specificity was obtained. Nutrient composition had a differential effect on hunger, fullness and food intake. Ratings of hunger decreased and fullness increased following the high starch and high protein preloads to a greater extent than after the high fat, high sucrose and mixed content preloads. When a self-selection meal was offered 2 hours after the preloads energy intake and preference for high carbohydrate and high fat food items were significantly decreased by the high protein and high starch preloads. However, no specific reduction in macronutrient intake was observed. In conclusion, differential effects of the preloads were observed in subjective ratings of hunger, fullness, preferences and subsequent food intake, but there was no indication that satiety was macronutrient-specific.

Adult↗
PubMed1988

Comparison of the effects of aspartame and sucrose on appetite and food intake.

We have studied the effects of consumption of foods sweetened with either sucrose or aspartame on appetite ratings and food intake. Normal weight, non-dieting subjects ate the same amount of high- and low-calorie versions of pudding or jello and despite the resulting difference in caloric intake, showed only a non-significant trend towards compensation in a lunch one or two hours later. There were no significant differences between rated hunger, fullness, desire to eat, the amount subjects wanted to eat, or sensory-specific satiety following the high- and low-calorie foods. Knowing the caloric values of the foods did not influence intake or appetite ratings in that both informed and uninformed subjects responded similarly. Thus in the short term subjects tended to eat a constant amount of a particular food and this volume had a greater effect on appetite ratings and subsequent intake than the calories consumed.

Appetite↗
PubMed1987

Response to upright exercise after myocardial infarction.

The left ventricular response to upright bicycle exercise was studied in 39 unselected, non-beta blocked patients (mean(SEM) age 54.2(1.7)yr) (mean(SEM) resting ejection fraction 41.9(2.3)%) 8-10 weeks after myocardial infarction. Nine healthy, age matched, sedentary adult men were studied for comparison (mean(SEM) age 49.8(0.9)yr). The stroke volume and cardiac output were measured by impedance cardiography at rest and after each 3 min workload until symptom limited maximum. The patients were separated into three groups based on stroke volume response to graded exercise. Group 1 (n = 14) had a normal stroke volume response to increasing heart rate. In group 2 (n = 13) stroke volume increased initially then decreased by greater than 15% at a heart rate greater than 100-105 beats.min-1. In group 3 (n = 12) stroke volume failed to increase during exercise. In group 1 cardiac output and mean arterial pressure increased whereas vascular resistance decreased during exercise in a normal fashion. Group 2 had an increased mean arterial pressure and systemic vascular resistance throughout exercise while heart rate increased in a similar fashion to group 1 until work of greater than 70 W was undertaken, at which time heart rate increased in a curvilinear fashion and cardiac output was attenuated. Group 3 had an attenuated cardiac output and a higher heart rate during exercise. In this group of patients systemic vascular resistance failed to decrease normally during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise Test↗
PubMed1986

Importance of considering ventricular function when prescribing exercise after acute myocardial infarction.

This investigation was undertaken in patients who had an acute myocardial infarction 12.6 +/- 0.4 months earlier to determine, using conventional methods, the nature of stroke volume changes during training regimens. Twenty-seven patients (mean age 52 +/- 2 years; rest ejection fraction 49 +/- 2%; New York Heart Association functional class I or II) and 9 normal, age-matched sedentary control subjects (mean age 50 +/- 1 years) exercised in the upright position on a bicycle ergometer. Stroke volume was measured by impedance cardiography at rest and after each workload. Ten patients (group A) had a stroke volume response similar to that of the normal sedentary subjects. In 8 patients (group B) the stroke volume increased initially, then decreased (more than 15%) at heart rates (HRs) greater than 100 to 105 beats/min. Nine patients (group C) had a flattened stroke volume response throughout exercise. Training HR determined by conventional methods corresponded to a maximal stroke volume in the normal subjects. Training HR in group A corresponded to a stroke volume that was maximal or near-maximal. Training HR in group B corresponded to a maximal or diminishing stroke volume. In group C, the training HR corresponded to a stroke volume no different from that at rest. Thus, training HR determined by conventional methods based solely on the chronotropic responses to exercise may place patients who have abnormal stroke volume responses to upright exercise in a situation during training sessions in which an inappropriately high HR, excessive fatigue or silent ischemia may develop.

Cardiography, Impedance↗
PubMed1985

Use of impedance cardiography in evaluating the exercise response of patients with left ventricular dysfunction.

Invasive studies in patients with left ventricular dysfunction show that data at rest (e.g. ejection fraction-EF) are poor predictors of the changes in cardiac output (CO) which occur with exercise. This investigation was undertaken to determine whether impedance cardiography could be used in such patients to assess CO response to exercise. The method was compared with the direct Fick method. Over a range of COs between 4 and 18 min-1 there was no systematic error. Reproducibility for CO over one week was highly significant (r = 0.94; P less than 0.001). Impedance cardiography was incorporated into routine exercise testing on a bicycle ergometer for a group of 15 patients (mean age 53.2 +/- 3.0 yrs, SEM) who had sustained a major myocardial infarct 6 to 12 months previously, (EF 38.1 +/- 3.5%, SEM). CO was measured at the end of each 3-min stage. In eight patients (EF 40.0 +/- 3.4%, SEM) CO response was abnormal with either a decrease or a failure to increase with increasing workloads. Conventional end-points i.e. angina, attainment of 85% of predicted maximum heart rate, abnormal blood pressure response or excessive dyspnoea did not indicate consistently a need to terminate the test. It is suggested that impedance cardiography is a useful non-invasive method of evaluating patients with left ventricular dysfunction.

Adult↗
PubMedDate not supplied

Comparison between flow cytometric and cytogenetic tumor cell DNA content using a simple flow sample preparation method: ploidy comparison of 86 fresh pediatric tumors.

A comparison of tumor ploidy by flow cytometry (FL) and cytogenetics (CYG) was made in 86 fresh pediatric solid (n = 47) and hematopoietic (n = 39) tumors using simple sampling and semiautomated proprietary FL preparation methods and defined histogram interpretive criteria. Tumor karyotypes with 44-48 chromosomes were regarded as CYG diploid and other chromosomal complements CYG aneuploid for comparison purposes. Five histograms were uninterpretable and nine cases failed to produce 15 or more metaphases for karyotyping. Mean G0/G1 peak coefficients of variation of all 86 cases were 2.7 and 3.0 for the diploid and aneuploid populations, respectively. Of the 72 eligible cases, 41 were concordant diploid and 16 concordant aneuploid with an overall concordance of 79%. The DNA index and karyotypic index correlation coefficient was 0.92 for the 16 concordant aneuploid cases. Analysis of the 15 discordant cases highlights the limitations of both methods and of the histogram interpretive criteria and indicates that FL is probably more sensitive for detection of tumor aneuploidy as defined and detected by these methods.

Aneuploidy↗