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Biomedical subjects

D M White

Publications and source records attributed to D M White.

At least 91 records · Page 5Linked to original sources

Social validation in competitive employment: evaluating work performance.

Social validation is a methodology utilized to evaluate the social acceptability of treatment goals, procedures, and results of applied interventions. This methodology lends itself well to assessing the work performance of mentally retarded individuals in nonsheltered employment settings, i.e., competitive employment. In this investigation, work evaluations provided by managers, shift supervisors, nonhandicapped co-workers, and mentally retarded workers (self) were analyzed. Results indicated significant differences across rater groups with regard to worker evaluation. Mentally retarded individuals rated their own work behavior most positively, followed by co-workers, shift supervisors, and managers, respectively. Rater groups disagreed particularly with respect to evaluating mentally retarded workers' job skills and interpersonal relationships in the job environment. Implications of these findings to the issues of concordance and consumer validation are discussed.

Adult↗

Immunohistochemical localization of substance P in postmortem rat and human spinal cord.

The stability of substance P-like immunoreactivity was examined in postmortem rat and human spinal cord using radioimmunoassay and indirect fluorescence immunohistochemistry. The distribution of fluorescence in rat and human spinal cord was unchanged at intervals up to 48 hours (h) and 87 h, respectively. Fine linear fluorescent fibers were seen only in rat spinal cord processed at time intervals up to two h postmortem; they were never observed in human spinal cord, which was routinely obtained more than 6 h postmortem. The content of substance P-like material in human spinal cord nd its immunohistochemical appearance was not affected by age, the nature of the terminal illness, or autopsy delay. However, no correlation was found between intensity of fluorescent staining and content as measured by radioimmunoassay. It may be possible to use postmortem analysis of substance P in diseases of the central nervous system, but radioimmunoassay and immunohistochemistry should be used concurrently.

Animals↗

Isoproterenol induced changes in myocardial nucleic acids.

Daily subcutaneous injections of isoproterenol increased heart weight 42% after 4 days of therapy. Ventricular RNA concentration was significantly elevated after 24 hours. Myocardial DNA was initially unchanged but significantly increased after 8 days of treatment. Ventricular systolic, diastolic pressures and coronary flow were not diminished in hypertrophied hearts. However, muscle contractility was slightly increased (P less than .05).

Animals↗

Effect of heating on lethality due to hyperthermia and selected chemotherapeutic drugs.

Because the rate of heating alters various cellular events associated with exposure to hyperthermia (including the rate of cell death), effect of this parameter on the cytotoxic interaction between selected anticancer drugs and hyperthermia was studied. The drugs cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, and adriamycin at 42.4 degrees C and bleomycin and methotrexate at 43 degrees C were tested in Chinese hamster ovary (CHO) cells in vitro. Heating times ranged from less than 3 minutes (immediate exposure) to 3 hours. For all drugs tested, synergistic cytotoxicity was not significantly altered by heating to peak temperature over 30 minutes as compared with immediate exposure. When heating to peak temperatures was prolonged to 3 hours, however, cell killing was markedly reduced, although significant sensitization to the drug remained. This was true despite the fact that, in CHO cells, heating to 42.4 degrees C over 3 hours produced no cell killing for up to 6 hours at that temperature. These results suggested that the mechanism(s) responsible for induced thermotolerance are probably different from those that cause cellular resistance to the cytotoxic effects of the drugs tested. These results may also partially explain the relative lack of clinical success with whole-body hyperthermia and chemotherapeutic drugs an anticancer treatment, because heating to therapeutic temperatures often requires 2-3 hours.

Animals↗

Experiential influences on the development of huddling preferences and "sibling" recognition in spiny mice.

The role of experience in the development of huddling preferences and sibling recognition by spiny mouse (Acomys cahirinus) weanlings was investigated. In the 1st experiment, pups separated from their littermates and fostered onto unfamiliar females (and their offspring) on the day of birth, Day 10, or Day 20, subsequently showed preferential huddling with their foster littermates. Huddling by biological siblings was as infrequent as huddling by unrelated, unfamiliar agemates. The 2nd study revealed that the mother may play a role in the ontogeny of sibling recognition, possibly through distinctive labeling of her offspring. We conclude that recognition of littermates develops through experience in the home cage in the absence of an inborn ability to recognize one's biological siblings.

Aging↗

Rate of heating as a determinant of hyperthermic cytotoxicity.

In Chinese hamster ovary cells and in normal and transformed rat embryonic fibroblasts, survival as a function of time at 42.4 degrees was dependent upon the rate of heating from 37 degrees to 42.4 degrees. Unexpectedly, the untransformed rat fibroblasts were more heat sensitive than were the transformed cells, and the protective effect of slow rates of heating upon survival at 42.4 degrees was also more pronounced in the normal cells than in the transformed cells. In Chinese hamster ovary cells, total cellular cholesterol content and cell volume were found to change significantly with time at 42.4 degrees when cells were heated immediately (37 to 42.4 degrees within 3 min) but did not vary significantly during 6 hr at 42.4 degrees in cells heated from 37 to 42.4 degrees over 3 hr. Chinese hamster ovary cells heated immediately to 42.4 degrees also showed a significant drop in the protein content of the particulate fraction with time at 42.4 degrees. In contrast, cells heated over 3 hr showed a significant increase in the protein content of the particulate fraction with time at 42.4 degrees. These data suggest that, if cells are heated to hyperthermic temperatures over sufficiently long intervals, mechanisms have time to develop which protect the cell membrane against changes associated with cell death in rapidly heated cells. The protective effect of slow rates of heating may partially explain the relative lack of success thus far observed with the use of whole-body hyperthermia in which heating from 37 degrees to 42 degrees often requires 2 to 3 hr.

Animals↗

Rapidity of compensatory lung growth following pneumonectomy in adult rats.

The rapidity with which lung growth was initiated following pneumonectomy was investigated using rats (330 g) in which lung weight-to-body weight ratio and lung cell size had stabilized. Following removal of the left lung, right lung weight increased from 823 to 1.161 mg within 7 days. Right lung weight in sham-operated animals did not change significantly. At day 7, right lung weight-to-body weight ratio in pneumonectomized rats was equal to that of both lungs in sham-operated animals; these values remained equal through day 14. Growth of individual lobes of the right lung was generally in proportion to their initial weights. Dry-to-wet weight ratio in either lung of sham-operated or pneumonectomized animals was unchanged, as compared to unoperated controls. Total right lung RNA and protein increased significantly by day 2 and reached levels equal to those in both lungs of sham-operated animals by day 7. Synthesis of lung proteins, estimated during 120 min of perfusion in situ, was elevated 25% on day 3. Incorporation of [3H]thymidine into DNA increased somewhat on day 2 and was elevated fourfold on day 3, corresponding with the initial accumulation of total DNA within the lung. These observations suggested that increased cell size may accompany early compensatory growth following pneumonectomy, but that the major portion of the response involved cellular hyperplasia.

Animals↗

Psychogeriatrics and community care.

The meaning of community care, as at present organised for the elderly mentally ill, is examined critically. It is argued that often the phrase is used to conceal the deficiencies of traditional institutional facilities, for which community care is apt to be regarded as a cheap substitute. It is suggested that it would be beneficial to have available true community care, capable of providing a full-time service to patients in their own homes, in preference to institutional facilities. Though such a scheme would benefit patients, it would have implications for the community discordant with present official attitudes.

Aged↗

Is winter depression a bipolar disorder?

Sixty-one winter depressive patients were evaluated for evidence of bipolar illness. Using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and the General Behavior Inventory, only nine (15%) could be considered bipolar. On prospective evaluation of patients during the summer following winter depression, few showed signs of manic or hypomanic symptoms. Also, few patients had a family history of bipolar illness. When patients were asked to evaluate symptoms of winter depression, lack of energy was found to be the most prominent feature of the syndrome.

Adult↗

An alternate splicing variant of the human telomerase catalytic subunit inhibits telomerase activity.

Telomerase, a cellular reverse transcriptase, adds telomeric repeats to chromosome ends. In normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to proliferative senescence. Introduction of the telomerase (hTERT) cDNA is sufficient to produce telomerase activity and immortalize normal human cells, suggesting that the repression of telomerase activity is transcriptional. The telomerase transcript has been shown to have at least six alternate splicing sites (four insertion sites and two deletion sites), and variants containing both or either of the deletion sites are present during development and in a panel of cancer cell lines we surveyed. One deletion (beta site) and all four insertions cause premature translation terminations, whereas the other deletion (alpha site) is 36 bp and lies within reverse transcriptase (RT) motif A, suggesting that this deletion variant may be a candidate as a dominant-negative inhibitor of telomerase. We have cloned three alternately spliced hTERT variants that contain the alpha, beta or both alpha and beta deletion sites. These alternate splicing variants along with empty vector and wild-type hTERT were introduced into normal human fibroblasts and several telomerase-positive immortal and tumor cell lines. Expression of the alpha site deletion variant (hTERT alpha-) construct was confirmed by Western blotting. We found that none of the three alternate splicing variants reconstitutes telomerase activity in fibroblasts. However, hTERT alpha- inhibits telomerase activities in telomerase-positive cells, causes telomere shortening and eventually cell death. This alternately spliced dominant-negative variant may be important in understanding telomerase regulation during development, differentiation and in cancer progression.

Alternative Splicing↗

Modern use of clomiphene citrate in induction of ovulation.

Clomiphene citrate is the treatment of first choice in the management of infertility in normally oestrogenized, anovulatory women (WHO group II). The majority of women with 'pure' anovulatory infertility respond to treatment with clomiphene citrate. The rates of pregnancy and miscarriage are close to those expected in a normal fertile population. Basal hormone concentrations do not predict outcome. An increased body mass index is the only factor which is consistently associated with a decreased response to clomiphene citrate; it follows therefore, that weight reduction should be an important part of therapy in anovulatory women. According to our data, only an increased luteinizing hormone value immediately post clomiphene citrate predicted an adverse pregnancy outcome in women who conceived. Clomiphene citrate, along with other ovulation induction therapies, can cause multiple follicular development, with a risk of ovarian hyperstimulation and multiple pregnancy. Ultrasound monitoring of treatment is important in order to choose the appropriate dose of clomiphene citrate in subsequent cycles and to minimize the risks of hyperstimulation and multiple pregnancy. When couples with other factors contributing to subfertility are excluded, the cumulative conception rate continues to rise after 6 months of treatment with clomiphene citrate, reaches a plateau by treatment cycle 12 and approaches that of the normal population. It has been reported that prolonged use of clomiphene citrate may be associated with an increased risk of a borderline or invasive ovarian tumour. Taking into consideration these observations, we recommend that anovulatory women responsive to clomiphene citrate should be treated for at least 6 cycles before considering more complex or invasive methods of ovulation induction, and that treatment should probably be limited to a maximum of 12 cycles.

Adult↗

Usefulness outcome in evaluating the utility of nuclear scans of the bone, brain, and liver in bronchogenic carcinoma patients.

In this study we employed the concept of the outcome audit to assess the "benefit" (in contrast to the number of positive readings) derived from 81 bone, 45 brain, and 47 liver scans, performed on 59 bronchogenic carcinoma patients. Benefit was rigorously defined and based on any outcome instrumental in the subsequent management of the patient. Clinically indicated scans were frequently found to be of benefit, while those without indications were not (88.0% vs. 12.5%). Negative scans were as useful as positive scans if clinically indicated (14.0% vs. 9.6%). Histology did not influence the likelihood of benefit. We conclude that scans obtained to evaluate a clinical abnormality are likely to be useful whether positive or negative while scans ordered without specific clinical indications are unlikely to be of management benefit.

Bone and Bones↗