Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the effects of interferon gamma (IFN-gamma) on very primitive hematopoietic progenitor cells, CD34(2+)CD38- human bone marrow cells were isolated and cultured in a two-stage culture system, consisting of a primary liquid culture phase followed by a secondary semisolid colony assay. CD34(2+)CD38- cells needed at least the presence of interleukin 3 (IL-3) and kit ligand (KL) together with either IL-1, IL-6, or granulocyte-colony-stimulating factor (G-CSF) in the primary liquid phase in order to proliferate and differentiate into secondary colony-forming cells (CFC). Addition of IFN-gamma to the primary liquid cultures inhibited cell proliferation and generation of secondary CFC in a dose-dependent way. This was a direct effect since it was also seen in primary single cell cultures of CD34(2+)CD38- cells. The proliferation of more mature CD34+CD38+ cells, however, was not inhibited by IFN-gamma, demonstrating for the first time that IFN-gamma is a specific and direct hematopoietic stem cell inhibitor. IFN-gamma, moreover, preserves the viability of CD34(2+)CD38- cells in the absence of other cytokines. IFN-gamma could, therefore, play a role in the protection of the stem cell compartment from exhaustion in situations of hematopoietic stress and may be useful as stem cell protecting agent against chemotherapy for cancer.
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PMID:Interferon gamma selectively inhibits very primitive CD342+CD38- and not more mature CD34+CD38+ human hematopoietic progenitor cells. 752 Apr 70

The prevalence and causes of 'burnout' and psychiatric disorder among senior oncologists and palliative care specialists have been measured in a national questionnaire-based survey. All consultant non-surgical oncologists in the UK were asked to participate. Sources of work-related stress and satisfaction were measured using study-specific questions which were aggregated into factors. Psychiatric disorder was estimated using the 12-item General Health Questionnaire. The three components of 'burnout'--emotional exhaustion, depersonalisation and low personal accomplishment--were assessed using the Maslach Burnout Inventory. Three hundred and ninety-three out of 476 (83%) consultants returned their questionnaires. The estimated prevalence of psychiatric disorder in cancer clinicians was 28%, and this is similar to the rate among British junior house officers. The study group had equivalent levels of emotional exhaustion and low personal accomplishment to those found in American doctors and nurses, but lower levels of depersonalisation. Among cancer clinicians, 'burnout' was more prevalent among clinical oncologists than among medical oncologists and palliative care specialists. Psychiatric disorder was independently associated with the stress of feeling overloaded (P < 0.0001), dealing with treatment toxicity/errors (P < 0.004) and deriving little satisfaction from professional status/esteem (P = 0.002). 'Burnout' was also related to these factors, and in addition was associated with high stress and low satisfaction from dealing with patients, and with low satisfaction from having adequate resources (each at a level of P < or = 0.002). Clinicians who felt insufficiently trained in communication and management skills had significantly higher levels of distress than those who felt sufficiently trained. If 'burnout' and psychiatric disorder among cancer clinicians are to be reduced, increased resources will be required to lessen overload and to improve training in communication and management skills.
Br J Cancer 1995 Jun
PMID:Burnout and psychiatric disorder among cancer clinicians. 777 99

From 1983 to 1993, 365 patients with obstructing endobronchial malignancies were treated by endobronchial high-dose radiation (HDR) iridium-192 afterloading. In 346 patients, the objective was palliation, and in 19, the objective was curative. A dose of 5 Gy at 10 mm from the source axis was administered on three (palliation) and four (cure) occasions, at intervals of 14 days. The majority of patients were treated after exhaustion of external beam radiation therapy (EBRT), often in conjunction with other interventional bronchologic modalities such as endobronchial laser resection. Of the patients, 65% had a squamous cell carcinoma. Endobronchial HDR brachytherapy results in few acute complications and can be performed with no major discomfort on an outpatient basis. In approximately 66% of patients, a palliative effect is achieved, even after the exhaustion of conventional treatment. Life may be prolonged for a few months, but the enhancement of survival is difficult to assess for several reasons. Mean survival is 9 months for limited disease and 5 months for extensive disease. Endobronchial HDR brachytherapy influences the pattern of failure: a 21% rate of fatal hemorrhages is probably the result of the selection of patients for this treatment rather than a treatment-related complication. There is sufficient evidence to suggest the rational use of HDR brachytherapy in combination with EBRT to effect a cure, or even on its own when tumor growth is strictly limited. However, the standardization of radiotherapy and endoscopic indications is an urgent priority. Prospective, controlled, and cooperative studies are mandatory. Endobronchial iridium-192 HDR brachytherapy complements endobronchial laser resection and is currently an established technique in the treatment of advanced malignant airway obstruction.
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PMID:Endobronchial radiation therapy for obstructing malignancies: ten years' experience with iridium-192 high-dose radiation brachytherapy afterloading technique in 365 patients. 756 85

A major reason for admission of community hospice clients to the hospital is exhaustion of the primary caregiver. One way to prevent the problem of caregiver exhaustion may be the use of trained laypersons who remain overnight with the ill person, thereby providing respite that allows the caregiver to sleep. A survey was conducted to assess primary caregivers' appraisal of the need for overnight respite and their willingness to receive this support from trained laypersons. Thirty-seven primary caregivers, who used the services of a community hospice, were interviewed to determine primary caregivers' appraisals of problems, resources, and needs. Ten (27%) primary caregivers reported usually receiving 0 to 4 of sleep per night and 27 (73%) reported receiving > 4 h. Sleep time was described by the majority as insufficient, but insufficient, sleep was statistically not a main reason for hospital admission. Findings suggested that those in the 0- to 4-h category were more vulnerable to exhaustion. Seventy percent of respondents indicated that they would use the services of a trained layperson for overnight respite and an additional 6% indicated that they would under certain conditions.
Cancer Nurs 1995 Oct
PMID:Need for overnight respite for primary caregivers of hospice clients. 758 87

A new assessment of quality of life (QOL) was made for cancer patients. The QOL assessment consists of 12 items: pain; nausea; constipation; general fatigue; sleep; eating; activity; a daily life pattern; conversation; treatment acceptability; satisfaction at the present status and family exhaustion. Ranges of scores are one (best) to five (worst). For visual expression of QOL, the author made an original method called "QOL diagram", drawn with a circle which has 12 diverging lines marked five points indicating the score for each item. QOL changes after cancer pain control with either oral or intravenous morphine were examined in 22 adult cancer patients by the QOL assessment. Laxatives and anti-nausea drugs were mostly prescribed at the same time in order to avoid side effects of morphine. QOL was evaluated and recorded by the author through an individual interview with each patient. It was observed that the psychological factors were improved along with pain relief. Although items such as general fatigue, nausea, constipation, sleep and eating did not change considerably at first, they improved well with time in the oral morphine group. On the other hand, there was no marked time-dependent change in the intravenous morphine group. Items such as activity, a daily life pattern and conversation were rather negative than positive. These items seem to be more important to improve QOL of the cancer patients, in particular, whose general status is relatively good. In conclusion, the QOL diagram helped us to follow subtle changes of status and needs of cancer patients. And it enables us to easily assess risks and benefits of the treatment plans including palliative care and home supportive programs. It is designed for both patients and medical staffs to use easily and repeatedly. However, the further evaluation and refinement will be needed to verify validity and reliability of the QOL diagram before a routine clinical application.
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PMID:[A new assessment of quality of life (QOL) for cancer patients]. 815 53

Acute and chronic bone marrow toxicities are the major limiting factors in the treatment of cancer. They are related to two factors. (i) The first is a decrease in the number of hematopoietic stem cells and progenitors caused by both a lethal effect of cytotoxic agents on these cells and by differentiation of stem cells provoked by a feed-back mechanism, itself induced by the depletion of more mature marrow compartments. (ii) The second factor is a reduction in self-renewal capacity of stem cells, which is also related to both direct (mutation) and indirect (ageing of stem cell population) effects. Stimulators and inhibitors of bone marrow kinetics play a prominent role in the induction of damage and recovery patterns. Acute effects can be circumvented by an increase in the number of cell divisions in the more mature compartments. This amplification is enlarged by the administration of hemopoietic growth factors which enhance regeneration and shorten the duration of blood aplasia. However, these stimulators may contribute to the exhaustion of the stem cell pool and they may increase the severity of late effects. Protection against chronic effects is difficult; however, the ability to 'switch on' and 'switch off' proliferation opens new avenues which are currently being explored. In particular, inhibitors may protect stem cells against early and late damage by maintaining them in a quiescent state during a course of radiotherapy or chemotherapy. Several inhibitors of hematopoietic stem cell proliferation have been identified during the past 5 years. AcSDKP (Seraspenide) was the first to be isolated and its protective effects against cytotoxic agents were described over a decade ago in mice. Its physiological role is now well established in mouse and man. Preliminary results of a Phase I-Phase II clinical trial strongly suggest that it may have a useful clinical role. Further research is necessary to assess the long-term protective effects of this new family of regulators.
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PMID:Ways of minimising hematopoietic damage induced by radiation and cytostatic drugs--the possible role of inhibitors. 829 82

Oncocytosis and oncocytomas have attracted attention because on the one hand there have been reports of the favourable prognosis and generally benign nature of oncocytic tumours, while on the other hand, Hurthle cell change in thyroid neoplasms have been reported to be correlated with aggressive biological behaviour and a significantly worse clinical course. Presently, there appear to be two schools of thought on the significance of oncocytosis: (i) a process where there is redifferentiation of cells with involvement in the pathogenesis of cancer; and (ii) a compensatory process for 'functional exhaustion' of the cell. Many aspects of oncocytosis seem unclear. In this study, transmission electron microscopy is used to demonstrate the presence of thyroid oncocytes in the hemithyroidectomy specimen of a patient with focal lymphocytic thyroiditis. Tissue sections from this specimen did not display preferential uptake of neutral red dye, a distinctive characteristic of M-phase cancer cells which was previously reported. The findings seem to suggest that oncocytes are not cells with distinctive proliferative potentials. If that were the case, then oncogenesis or cancer cell progression and oncocytosis may not be convergent processes.
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PMID:Oncocytes of the thyroid: a neutral red dye uptake study. 833 84

Partial regression in cutaneous malignant melanoma has been reported by a number of observers, albeit not all, to be associated with a relatively poor prognosis; in contrast, a keratoacanthoma, which eventually regresses, does not metastasize. The Hammond effect could explain the possibly poor prognosis of the thin regressing melanoma. Hammond(W.G. Hammond et al., Cancer J., 8: 130-138, 1995) showed that the speed of biological progression to less differentiated phenotypes is directly related to the immunocompetences of the tumor hosts. If partial regression is a sign of an unusually strong immune reaction, then the melanoma that partially regresses might have a relatively poor prognosis because of the greater risk of biological progression among the surviving tumor clones. A Hammond effect is not associated with regression of a keratoacanthoma. I postulate that the growth of this tumor is accelerated, rather than restrained, by the immune reaction and that the ultimate regression of the tumor is the result, not of immune cytotoxicity, but of a rapid terminal differentiation (a reverse Hammond effect); alternatively, very rapid growth might lead to an exhaustion of growth potential before progression to clonal immortality could occur.
Cancer Res 1996 Mar 01
PMID:The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma. 864 Jul 80

Apoptosis is an important cellular process by which superfluous or unwanted cells are deleted from an organism during tissue remodeling and differentiation. Recent studies have demonstrated the role of this programmed cell death or "controlled cell suicide" in the physiological function of an organism. Suppression of apoptosis increases the susceptibility of an individual to malignancy whereas uncontrolled cell death is associated with degenerative diseases. Normal development of both female and male gonads is characterized by massive cell death. More than 99% of ovarian follicles endowed at early life are destined to undergo apoptosis and the exhaustion of these follicles serves as a "clock" for female reproductive senescence. In the testis, up to 75% of male germ cells also undergo apoptosis, perhaps as a mechanism to delete superfluous or defective germ cells. Gonadal cell apoptosis provides valuable models to study hormonal regulation of apoptosis. In the ovary, gonadotropins, estrogens, growth hormone, growth factors (IGFI, EGF/TGF-alpha, basic FGF), cytokine (interleukin-1 beta) and nitric oxide act in concert to ensure the survival of preovulatory follicles. In contrast, androgens, interleukin-6 and gonadal GnRH-like peptide are apoptotic factors. Developmental studies further indicate that fractions of endowed follicles are recruited throughout the reproductive life whereas most of the primordial follicles are "arrested" at the initial stage of development for a prolonged time. Because a transcriptional factor WT1 is expressed in high levels in follicles at early stages of development and because WT1 over-expression represses the promoter activity of inhibin-alpha gene, this nuclear protein may be important in the maintenance of follicles at early stages of development. Once a cohort of follicles is recruited to grow, it is destined to undergo apoptosis unless rescued by survival factors. After puberty onset and under gonadotropin stimulation, some of the growing antral follicles are "selected" to continue their final maturation and secrete high levels of estrogens to trigger ovulation. Following repeated cycles of recruitment, atresia or ovulation, the follicle reserve is exhausted, thus signaling the onset of reproductive senescence. Although the somatic granulosa cell is the major cell type undergoing apoptosis in the ovary, the germ cells in the testis also exhibit signs of apoptotic cell demise. In the testis, gonadotropins and androgens act as survival factors whereas exposure to elevated temperature in cryptorchid testes increases apoptosis. In the seasonally breeding hamster model, photoperiod-entrained regression and recrudescence of testis tissue serves as a unique natural model of apoptosis. With recent advances in our understanding of the cellular mechanism of apoptosis, including the elucidation of the Ced9/bc12 and Ced3/ICE family of proteins, further investigation of gonadal apoptosis may lead to a better understanding of gonadal degenerative disorders (such as premature ovarian failure and oligospermia), reproductive senescence and tumorigenesis. The gonadal model should also be valuable in studying the regulation of intracellular apoptosis genes by external hormonal signals.
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PMID:Gonadal cell apoptosis. 870 Oct 90

Psychological stress and work-related burnout in staff working with AIDS and with cancer patients were compared using a self-report method of assessment. Measures included the General Health Questionnaire (GHQ), Maslach Burnout Inventory (MBI), and the Social Adjustment Scale (SAS-M). More than 80% of those staff who were approached responded to the questionnaire, including 70 doctors and nurses working with people with AIDS and 41 doctors and nurses working in oncology. More than a third of staff had substantial levels of psychological morbidity, and about a fifth had significant levels of work-related stress. Factors associated with the presence of high levels of psychological morbidity and with abnormal levels of emotional exhaustion, depersonalization, and concerns about personal accomplishment were identified. Staff described the work situations with which they had difficulty dealing and some of the coping strategies they used. The findings confirm that staff working with people with cancer or AIDS experience psychological difficulties of the kind likely to respond to interventions aimed at improving their ability to cope with work-related stresses. The mental health services could play an important role in carrying out research in this field and in providing practical help to deal with staff's difficulties.
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PMID:The psychological impact on staff of caring for people with serious diseases: the case of HIV infection and oncology. 873 23


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