How do relatives remember the dying of lung cancer patients after 2-8 years? A qualitative study based on in-depth interviews with family members

Background. The aim of our study was to assess how relatives remember the dying of lung cancer patients several years after their death. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with 2 researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire and to score the Quality of Dying Apgar. Results. Family members of 15 of the patients stated recognizing the dying of their loved one. They concluded this on the basis of exacerbation of symptoms, "typical" appearance, change in behaviour or particular words the patient said to them. The median score of the quality of dying was 6.5/10 (range 3-9). Lower scoring was observed for patients who died in hospital, without the family present at the moment of death and with uncontrolled symptoms. Only 5 of the relatives assessed pain and other symptom control as satisfactory. Other family members remembered pain (n = 9), dyspnoea (n = 8), delirium (n = 4) and other symptoms as disturbing the dying in a severe or moderate way. Three relatives assessed that their loved one's dying was not "dignified", mostly due to the severe physical suffering, the nursing being crucially remiss at the hospital and the patient's being alone at the moment of death. All family members were able to describe the healthcare professionals' attitudes and even repeat the statements they heard from them. Conclusion. We have demonstrated that several years after death many of the words and the behaviour of the dying patients were still alive in their relatives' memories. The family members remember how the healthcare professionals behaved and what they said to them. While caring for dying people, we should bear in mind that the way in which we behave may either give strength to the family or destroy their peace of mind for many years.Background. The aim of our study was to assess how relatives remember the dying of lung cancer patients several years after their death. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with 2 researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire and to score the Quality of Dying Apgar. Results. Family members of 15 of the patients stated recognizing the dying of their loved one. They concluded this on the basis of exacerbation of symptoms, "typical" appearance, change in behaviour or particular words the patient said to them. The median score of the quality of dying was 6.5/10 (range 3-9). Lower scoring was observed for patients who died in hospital, without the family present at the moment of death and with uncontrolled symptoms. Only 5 of the relatives assessed pain and other symptom control as satisfactory. Other family members remembered pain (n = 9), dyspnoea (n = 8), delirium (n = 4) and other symptoms as disturbing the dying in a severe or moderate way. Three relatives assessed that their loved one's dying was not "dignified", mostly due to the severe physical suffering, the nursing being crucially remiss at the hospital and the patient's being alone at the moment of death. All family members were able to describe the healthcare professionals' attitudes and even repeat the statements they heard from them. Conclusion. We have demonstrated that several years after death many of the words and the behaviour of the dying patients were still alive in their relatives' memories. The family members remember how the healthcare professionals behaved and what they said to them. While caring for dying people, we should bear in mind that the way in which we behave may either give strength to the family or destroy their peace of mind for many years

The last months of lung cancer patients’ lives, in the memory of their relatives. A qualitative study based on in-depth interviews with family members

Background. The aim of the study was to assess how family members remember the final months of their loved ones 2–8 years after their death. We focused particularly on their recognition of the patients’ physical, psychosocial and spiritual needs. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with two researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire. Results. Almost all the relatives interviewed in our study were able to recognize the beginning of the terminal phase. They connected the beginning of dying with the deterioration of the physical and/or psychological status of patients, such as the exacerbation of weakness and/or other symptoms or with clearly distinguished incidents such as cancer recurrence or hip fracture. The majority were able to define the length of this phase as being several months (median = 3, range 1–11 months). The most common physical symptoms mentioned by the relatives interviewed were, in sequential order: pain (n = 13) and fatigue (n = 13), anorexia (n = 9), dyspnoea (n = 7) and cachexia (n = 7). Of the 20 decedents, 18 regularly received painkillers at least at some period during their final months. Apart from medicines prescribed by the doctors, 9 patients were treated with “anticancer” herbs, or homeopathy, or by bioenergotherapy. From the relatives’ perspectives, the main approach was focused on the physical aspects of care while there was a lack of psychological and social support, the latter often causing severe financial burden. Most relatives believed that chaplains are the main source of spiritual comfort and there was easy access to such a service both in their parish and in the hospice or hospitals. Conclusion. Our study showed that the families remembered feelings of loneliness and helplessness when confronted with the psychological suffering of their loved ones and the financial burdens caused by the caregivers. Professionals involved in palliative care should acknowledge that holistic care requires sensitivity, not only to the physical but also to the psychosocial and spiritual aspects of end-of-life care.Background. The aim of the study was to assess how family members remember the final months of their loved ones 2–8 years after their death. We focused particularly on their recognition of the patients’ physical, psychosocial and spiritual needs. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with two researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire. Results. Almost all the relatives interviewed in our study were able to recognize the beginning of the terminal phase. They connected the beginning of dying with the deterioration of the physical and/or psychological status of patients, such as the exacerbation of weakness and/or other symptoms or with clearly distinguished incidents such as cancer recurrence or hip fracture. The majority were able to define the length of this phase as being several months (median = 3, range 1–11 months). The most common physical symptoms mentioned by the relatives interviewed were, in sequential order: pain (n = 13) and fatigue (n = 13), anorexia (n = 9), dyspnoea (n = 7) and cachexia (n = 7). Of the 20 decedents, 18 regularly received painkillers at least at some period during their final months. Apart from medicines prescribed by the doctors, 9 patients were treated with “anticancer” herbs, or homeopathy, or by bioenergotherapy. From the relatives’ perspectives, the main approach was focused on the physical aspects of care while there was a lack of psychological and social support, the latter often causing severe financial burden. Most relatives believed that chaplains are the main source of spiritual comfort and there was easy access to such a service both in their parish and in the hospice or hospitals. Conclusion. Our study showed that the families remembered feelings of loneliness and helplessness when confronted with the psychological suffering of their loved ones and the financial burdens caused by the caregivers. Professionals involved in palliative care should acknowledge that holistic care requires sensitivity, not only to the physical but also to the psychosocial and spiritual aspects of end-of-life care

Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action

We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity

Regulation of genes encoding proteolytic enzymes during mammary gland development

The mammary gland undergoes extensive tissue remodelling during each lactation cycle. During pregnancy, the epithelial compartment of the gland is vastly expanded (Benaud et al. 1998). At the end of lactation the epithelial cells undergo apoptosis and adipocyte differentiation is induced (Lilla et al. 2002). Ductal and alveolar growth during puberty and pregnancy, and the involution process require the action of proteolytic enzymes (including matrix metalloproteinases, plasminogen and membrane-peptidases) and the corresponding genes are activated during these periods (Benaud et al. 1998; Alexander et al. 2001). Matrix metalloproteinases (MMP) are expressed in several cell types of the mammary gland including stromal fibroblasts (e.g., MMP3, MMP2), epithelial cells (e.g., MMP7 or MMP9), adipocytes (e.g., MMP2) and lymphoid cells (e.g., MMP9) (Crawford et al. 1996; Lund et al. 1996; Wiseman et al. 2003). A number of knock-out mice, which are deficient for individual MMP genes (e.g., MMP2, MMP3) or plasminogen, display alterations to mammary gland structure and impairment of lactation (Lund et al. 1999; Wiseman et al. 2003)

IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response

Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial-mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT and fibroblast activation and is considered to be a major pro-fibrotic factor. Recently, IGFBP-5 [IGF (insulin-like growth factor)-binding protein-5] has also been shown to induce similar effects on TGFβ1, and is strongly implicated in the process of senescence. It also stimulates migration of peripheral blood mononuclear cells, implicating it in the inflammatory response. In this paper, we examine the evidence for a role of IGFBP-5 in fibrosis and highlight its structural relationship with other matrix proteins and growth factors also implicated in tissue remodelling