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Biomedical subjects

M A Stephens

Publications and source records attributed to M A Stephens.

At least 55 records · Page 3Linked to original sources

Synthesis and evaluation of novel electrophilic nitrofuran carboxamides and carboxylates as radiosensitizers and bioreductively activated cytotoxins.

A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on hypoxic V79 cells. The compounds were extremely efficient radiosensitizers of such cells in vitro and were more efficient than known nitroimidazoles of similar type. Their efficiencies as radiosensitizers correlated with their high electron affinity (E7(1] as measured by pulse-radiolysis. However the compounds showed little radiosensitizing activity towards KHT sarcomas in C3H mice. The compounds in this series of nitrofurans were generally more toxic towards hypoxic cells than towards oxic cells in vitro but were less effective upon the basis of a differential effect than were similar nitroimidazoles reported previously.

Amides↗

The impact of family interactions on recovery from stroke: help or hindrance?

The family networks of 47 geriatric stroke patients were examined for social supports and social problems as they related to well-being after hospital discharge. Structured interviews assessed positive and negative family interactions and patients' independence in activities of daily living (ADL), time use, personal adjustment, and cognitive functioning. After controlling for patients' medical status at hospital discharge, social supports were not associated with any of the outcomes examined. Social problems explained additional variance in personal adjustment and ADL independence.

Activities of Daily Living↗

Emotional and somatic consequences of binge episodes.

The present study investigated emotional and somatic consequences of the daily eating episodes of 19 bulimics, 15 bingers, and 20 normal control subjects. For 1 week, subjects rated 21 emotional and somatic states immediately following all eating episodes and 1 h later. Results indicated that bulimics and bingers reported significantly greater negative and somatic consequences immediately following their binge episodes than normal eaters following all of their eating episodes. For both groups, these negative emotional consequences persisted over time. Following nonbinge episodes, only bulimics reported experiencing significantly greater negative emotions than normal controls. Comparisons of the binge and nonbinge episodes of the bulimics and bingers indicated that binge episodes are followed by greater immediate and delayed negative and somatic consequences than nonbinge episodes. Furthermore, the positive emotions that occur immediately after a binge significantly decrease in intensity within 90 min after the episode. Theoretical and clinical implications of these findings are discussed.

Adaptation, Psychological↗

The differential hypoxic cytotoxicity of bioreductive agents determined in vitro by the MTT assay.

We obtained good agreement between the MTT assay and conventional clonogenic assays regarding the concentration and contact time required to produce a given level of killing of Chinese hamster V79 cells treated in either air of N2 with a range of bioreductive cytotoxic drugs. All agents chosen for these experiments represented classes of compounds known to be more toxic towards hypoxic cells than they are to aerobic cells. Namely a quinone, mitomycin C; a di-N-oxide, SR4233; and a number of nitro-heterocyclics including misonidazole. The MTT assay is carried out with V79 cells attached to the bottom of 1 cm glass wells within a 24 well plate. All procedures, that is drug exposure, cell growth, metabolism of MTT are then carried out in situ. To measure optical density we used an ELIZA plate reader modified to take 24-well plates. We propose that this method provides a simple, rapid procedure for evaluating the cytotoxicity of bioreductive drugs.

Animals↗

Hassles and uplifts of giving care to a family member with dementia.

The role of daily caregiving stressors (hassles) and small caregiving satisfactions (uplifts) in the well-being of 60 family caregivers was investigated. Hassles and uplifts in 4 domains of caregiving were examined, and direct effects of hassles, uplifts on caregivers' social and psychological well-being, as well as the interactive and net effects of hassles and uplifts, were assessed. Hassles associated with care recipients' behavior demonstrated strongest associations with well-being. Women and caregivers to socially responsive yet behaviorally inappropriate care recipients reported more behavior and cognitive hassles. Uplifts associated with assistance in activities of daily living and with care recipients' behavior were related to well-being, with more uplifts related to greater, rather than less, depression. More intensely involved caregivers reported more of these uplifts. Net effects in the hypothesized direction were found, but no interactive effects emerged.

Activities of Daily Living↗

Caregiving Hassles Scale: assessing the daily hassles of caring for a family member with dementia.

Examined was a scale designed to assess the daily hassles of caring for a family member with Alzheimer's Disease (AD). Primary caregivers to AD patients (N = 60) completed the Caregiving Hassles Scale on two occasions and reported on their well-being. The 42-item scale provides a reliable and psychometrically sound instrument for assessing hassles associated with assistance in basic ADL, assistance in instrumental ADL, care-recipients' cognitive status, care-recipients' behavior, and caregivers' social network.

Activities of Daily Living↗

Hypothyroidism: effect on warfarin anticoagulation.

Although our observation is not the first case of reduced PT response to oral anticoagulants associated with hypothyroidism, it is the only such interaction reported since 1963, and the first case involving warfarin therapy in a human being. We submit this case as a reminder of a potentially forgotten interaction, and to stress the importance of close monitoring in patients receiving warfarin therapy who have concomitant changes in thyroid function.

Administration, Oral↗

Family caregiving to dependent older adults: stress, appraisal, and coping.

Articles presented in this 1987 APA symposium adopt a stress, appraisal, and coping framework for conceptualizing the experience of family caregiving. Each article emphasizes 2 themes: (a) caregivers' adaptation to the chronic demands of in-home caregiving and (b) factors that mediate the relationship between caregiving stress and caregiver's adaptation. The articles presented in this symposium illustrate both the utility of this theoretical approach to studying caregiving stress and the difficulty inherent in its use.

Adaptation, Psychological↗

3-Nitro-1,2,4-triazoles as hypoxia-selective agents.

A series of 1-alkyl-3-nitro-1,2,4-triazoles has been prepared and assessed in vitro as radiosensitizers of hypoxic cells and as bioreductive cytotoxins. The differential hypoxic:aerobic cytotoxicities of representative compounds have been determined and compared with analogous 2-nitroimidazoles. It is found that the 3-nitrotriazoles are considerably less effective than the corresponding 2-nitroimidazole derivatives. This result includes dual-function nitrotriazoles where potential alkylating moieties have been incorporated into the molecule. In contrast, the 3-nitrotriazoles show similar or slightly improved radiosensitizing efficiency, in accord with their redox behaviour, and significantly lower chronic aerobic toxicity compared with the corresponding 2-nitroimidazoles. On the basis of a derived in vitro therapeutic ratio, 1-(3-nitro-1,2,4-triazol-l-yl)-3-piperidino-2-propanol (8) has been identified as particularly active and warrants further evaluation as a hypoxic cell radiosensitizer in vivo.

Animals↗

Effects of daily activities and social behavior on blood-pressure elevation.

This study examined the effects of daily activities and social behavior on the blood-pressure elevation in 21 normotensives, 20 borderline hypertensives, and 20 sustained essential hypertensives. Blood pressures were recorded over a 24-hr period using an ambulatory monitor while subjects recorded their daily activities and social involvement at each cuff inflation. Results indicated that only a moderate proportion of the blood pressure readings of the two clinical groups exceeded 140/90 mm Hg. Results also suggested that the blood pressures of normotensives were more responsive to changes in physical activity, while the blood pressures of sustained hypertensives were more responsive to social involvement. When group differences emerged on mean blood-pressure elevation, analyses indicated that the two hypertensive groups frequently differed from the normotensive group but rarely from each other. The results suggest that differences in blood-pressure elevation cannot be fully understood without considering behavior and support its continued inclusion in the study of blood pressure.

Activities of Daily Living↗

Stressful situations in caregiving: relations between caregiver coping and well-being.

We examined ways in which caregivers cope with stressful caregiving situations and the relations between coping strategies and caregivers' psychosocial well-being. Respondents were 58 family caregivers to patients discharged from a rehabilitation hospital. Caregivers identified a recent stressful event in caregiving and indicated strategies used to cope with this event. After controlling for patients' impairment level, analyses indicated that caregivers engaging in more escape-avoidance coping reported greater depression and more conflict in their personal relationships. Those using more positive reappraisal demonstrated greater positive affect. Younger caregivers, many of whom were women, used more avoidance strategies. Results have implications for therapeutic interventions with family caregivers.

Activities of Daily Living↗

Dual-function radiation sensitizers and bioreductive drugs: factors affecting cellular uptake and sensitizing efficiency in analogues of RSU 1069.

Alkyl aziridine analogues of the hypoxic cell radiosensitizer RSU 1069 have been synthesized and one of these, RB 7040, containing the tetramethyl substituted aziridine, is a more efficient sensitizer in vitro than RSU 1069 (Ahmed et al., 1986). The extent to which variation in drug uptake can influence the sensitizing efficiency of RSU 1069 and its analogues has been investigated by determining the cellular uptake of these weakly basic sensitizers as a function of the pH of the extracellular medium (pHe) over the range 5.4-8.4. Following exposure of V79 cells to these agents for 1 h at room temperature, the ratio of intra- to extracellular concentration (Ci/Ce) was near unity at pH 5.4. Increasing pHe to 8.4 resulted in no change in the ratio Ci/Ce for RSU 1069 (pKa = 6.04). In contrast, the values of Ci/Ce increased three-fold for RSU 1165 (pKa = 7.38) and eleven-fold for RB 7040 (pKa = 8.45). Radiosensitization by RSU 1069 showed little dependence on pHe over the range studied, whereas increasing pH caused an apparent increase in sensitizing efficiency of both RSU 1165 and RB 7040. However, when the enhancement ratios for sensitization were normalized to take account of the effect of extracellular pH on drug uptake, efficiency of sensitization was independent of pHe. This study suggests that changes in basicity (pKa) may have wider potential for therapeutic exploitation on the basis of selective tumour uptake for this type of agent.

Animals↗

Emotional reactivity and eating in binge eating and obesity.

The present study investigated daily mood fluctuations and moods during eating in normal and overweight binge and nonbinge eaters (N = 56) and moods during binge and nonbinge episodes of individuals who binge eat (N = 29). For 2 weeks, subjects completed the Multiple Affect Adjective Checklist each morning and continuously recorded the mood during eating and the type and quantity of food eaten during each eating episode. The results indicated that bingers experience greater fluctuations of anxiety and depression than nonbingers and overweight individuals experience greater fluctuations in anxiety, hostility, and depression than normal-weight individuals. In addition, for bingers, negative mood states are experienced during a significantly greater proportion of binge episodes than nonbinge episodes, although the intensity of the negative mood state was not related to the severity of the binge-eating episode. Theoretical and clinical implications of these findings are discussed.

Adult↗

Behavioral predictors of blood pressure variation in hypertensives and normotensives.

This study examined the relative impact of five behavioral factors--activity, posture, location, social involvement, and tension--on the 24-hr blood pressure (BP) variability of 21 normotensives, 18 borderline hypertensives, and 18 sustained essential hypertensives. Multiple-regression analyses indicated that within each diagnostic group, activity accounted for more variance in BP variability than any other behavioral dimension. For each behavioral dimension examined, the magnitude of the relationship with BP was generally greater for the normotensives than for both hypertensive groups. In contrast, variation due to individuals was a better predictor of BP variability for the two hypertensive groups than for the normotensive group. Number of months hypertensive and use of antihypertensive medication were related to BP variability for the sustained hypertensive group. Findings have implications for the use of ambulatory BP monitors and interpretation of resulting data.

Activities of Daily Living↗

Social networks as assets and liabilities in recovery from stroke by geriatric patients.

Interactions in the social networks of 48 elderly stroke patients were examined as factors influencing outcomes after hospital discharge. Structured interviews assessed the frequency of perceived positive and negative interactions, as well as patients' behavioral independence, time use, personal adjustment, and cognitive functioning. Negative interactions occurred less frequently than positive ones. After controlling for status at hospital discharge, negative and positive interactions differentially explained variance in morale, psychiatric symptoms, and cognitive functioning. Although negative interactions were associated with poorer morale and greater psychiatric symptoms, positive interactions were associated with less mental confusion. Patients' reporting and not reporting negative interactions did not differ significantly on a variety of social and demographic variables previously shown to predict social interactions and well-being. Findings indicate that social interactions may both impede and facilitate rehabilitation for older adults and have implications for both theories of social support and the design of therapeutic interventions.

Activities of Daily Living↗

Predictors of psychotherapy outcome for children at a community mental health center.

This study assessed the utility of multiple predictors of outcome for 268 child clients and their families who received psychotherapy at a community mental health center for children. Outcome was measured by the number of therapy sessions attended, the length of therapy, and improvement ratings of the child and family made by independent judges. Regression analyses revealed that the strongest predictors of outcome were previous exposure to therapy, therapist type (permanent professional staff vs. intern), family constellation, therapist experience, and referral source. Implications for treatment planning and future research are discussed.

Child↗

Integrable alpha-amylase plasmid for generating random transcriptional fusions in Bacillus subtilis.

An integrable plasmid, pOK4, which replicated independently in Escherichia coli was constructed for generating transcriptional fusions in vivo in Bacillus DNA. It did not replicate independently in Bacillus subtilis, but it could be made to integrate into the chromosome of B. subtilis if sequences homologous to chromosomal sequences were inserted into it. It had a selectable marker for chloramphenicol resistance and carried unique sites for EcoRI and SmaI just to the 5' side of a promoterless alpha-amylase gene from Bacillus licheniformis. When B. subtilis DNA fragments were ligated into one of these sites and the ligation mixture was used to transform an alpha-amylase-negative B. subtilis strain, chloramphenicol-resistant transformants could be isolated conveniently. Many of these were alpha-amylase positive, owing to the fusion of the plasmid amylase gene to chromosomal operons. In principle, because integration need not be mutagenic, it is possible to obtain fusions to any chromosomal operon. The site of each integration can be mapped, and the flanking sequences can be cloned into E. coli. The alpha-amylase gene can be used to detect regulated genes. We used it as an indicator to detect operons which are DNA-damage-inducible (din), and we identified insertions in both SP beta and PBSX prophages.

Bacillus subtilis↗