Cell proliferation and ku protein expression in ageing humans.

Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku protein in a human population of 43 subjects of different ages. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the early steps of DNA damage recognition. In the present study, PBL from subjects of different ages were PHA-activated to evaluate the stimulation index and the production of Th1- and Th2-type cytokines. Moreover, nuclear extracts were obtained from activated lymphocytes to evaluate by a gel retardation assay the presence and the functional activity of the heterodimer ku 70/80. Our results indicate that ageing affects the mitotic responsiveness and cytokine production to a significant extent, but only marginally the expression of ku 70/80. These findings suggest that the age-related impairment in DNA repair mechanisms are only in part related to the reduced expression of ku protein able to recognize DNA damage.

Immune parameters in a population of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations.

Twenty-six institutionalized elderly subjects, selected as healthy according to the SENIEUR protocol, were compared to adult controls to establish correlations between affective disorders and immune abnormalities and to investigate underlying neuroendocrine mechanisms. After an extensive psychodiagnostic examination, 35% of the aged subjects were classified as depressed. Cutaneous delayed hypersensitivity tests showed reduced responses in the aged, but no correlation was found with the psychological status. Examination of the peripheral blood lymphocyte subsets revealed no imbalance in the percentages of CD3+, CD4+, CD8+ cells in the aged. A slight reduction in the CD4+/CD8+ cell ratio could however be detected in the non-depressed aged, as compared to adult controls. The CD4+/CD45R+ cell subset was reduced in non-depressed aged. The percentage of B lymphocytes was reduced in the aged, mostly in the non-depressed subjects. No changes were detected in the percent of OKDR+ cells. The percentage of CD16+ cells was found unchanged, while that of Leu7+ cells was significantly higher in the aged than in the adults and in the non-depressed than in the depressed aged. Leu7+ cell levels were negatively correlated with the depression score. On double labelling, the percent of CD16+/Leu7+ cells appears increased in the subgroup of depressed aged and positively correlated with age. Plasmatic and urinary cortisol levels were both positively correlated with depression score. Urinary cortisol level was higher in the depressed aged. These parameters, as well as plasmatic ACTH, beta-endorphin and urinary catecholamines, were not correlated with immune responses. Based on these findings, we recommend that the neuroendocrinological conditions should be taken into account when healthy subjects are examined in studies of immune senescence.

Impairment of lymphocyte activities in depressed aged subjects.

Lymphocyte activities were determined in a population of 26 institutionalized aged subjects, selected as healthy according to the SENIEUR protocol and previously reported to display immunological and endocrinological abnormalities correlated with depressive disorders. The lymphocyte mitotic response to PHA, which was reduced in aged as compared to adult subjects, was found to be significantly lower and negatively correlated with the depression score in the elderly subjects. In supernatants of PHA-stimulated lymphocyte culture from aged subjects, IL-2, IL-4 and gamma-IFN levels were very low and more severely affected in the depressed aged group. Each cytokine production was negatively correlated with age and depression score. NK activity was lower in the aged and it could be augmented by the addition of IL-2 or alpha-IFN, even though to a lesser extent than in the adult subjects. The nondepressed aged displayed higher levels of IL-2 inducible NK activity than the depressed aged subjects. IL-2 and alpha-IFN stimulated NK activities were negatively correlated with depression score. The present work indicates that the psychological status could affect lymphocyte reactivity in the aged. Given the relatively high frequency of affective disorders in these subjects, the psychological status should be considered in studies of immune senescence.

Changes in the amount and level of phosphorylation of p56(lck) in PBL from aging humans.

The effects of aging on the activation of the cytoplasmic tyrosine protein kinase p56(lck) have been investigated in PBL from adult and elderly subjects upon activation with mitogens or different co-stimuli. Results show that the amount and phosphorylation of p56(lck) are reduced in PBL from elderly as compared to adult subjects. This finding suggests that alterations in p56(lck) may contribute to the age-associated loss of some T cell functions, such as proliferation and IL-2 production, which are found decreased in PBL from old individuals. However, p56(lck) seems irrelevant to the production of IFN-gamma and IL-4 which were both found increased in the PBL from old subjects, as expected from the relative expansion of memory versus naive T cell subpopulations in aging.

Neuroimmunomodulation and psychoneuroendocrinology: recent findings in adults and aged.

In recent years the relationships among immune, endocrine and nervous systems have been extensively studied, and grouped in a new research field: psychoneuro-immunoendocrinology. Since ancient times its has been known that, in humans, mood as well as environmental influences could affect health. In the late '70s, only, evidence of bi-directional pathways has been achieved, first in animal models and, later on, in humans. We reviewed current knowledge on neuroimmunomodulation, concerning the influence of stress and psychological status on immunity as well as neuroendocrine modulation by the immune system, reporting some data obtained from our studies. Particularly, having detected a relevant impairment concerning most of the parameters studied, we emphasized the effects of depressive disorders on immune function in the elderly.

Psychological status and immunological parameters of institutionalized aged.

In the elderly, an impairment of the immune system could lead to increased incidence of infectious, neoplastic and autoimmune diseases; on the other hand, depression, which is the most common psychiatric problem in aged people, seems to be linked with alterations in immunological function. Thirteen institutionalized elderly subjects were studied to investigate the relationship between depression and immunological parameters. These subjects were selected as "healthy" according to the SENIEUR-EURAGE protocol and they belonged to a population already evaluated by our group--one year before--for psychological, endocrinological and immunological parameters. The lymphocyte mitotic response to PHA was greatly diminished in aged subjects, when compared to the adult controls. Depressed elderly showed impaired immunological function as compared with nondepressed ones, either "in vitro" or "in vivo". Lymphocyte stimulation with phytohemagglutinin (PHA), T cell growth factor (TCGF) production (induced by stimulation with PHA) and cutaneous delayed hypersensitivity (CDH) were reduced in depressed aged subjects. As far as lymphocyte proliferation with PHA in the whole group were concerned, no differences were found comparing the present results with those obtained in a former study. Although it is difficult to understand the significance of the immune imbalance associated with depression in the elderly, our results suggest that psychological status could influence the immunological functions in old people.

The professional autonomy of the medical doctor in Italy.

This contribution deals with the issue of the professional autonomy of the medical doctor. Worldwide, the physician's autonomy is guaranteed and limited, first of all, by Codes of Medical Ethics. In Italy, the latest version of the national Code of Medical Ethics (Code 1998) was published in 1998 by the Federation of provincial Medical Associations (FnomCeO). The Code 1998 acknowledges the physician's autonomy regarding the scheduling, the choice and application of diagnostic and therapeutic means, within the principles of professional responsibility. This responsibility has to make reference to the following fundamental ethical principles: (1) the protection of human life; (2) the protection of the physical and psychological health of the human being; (3) the relief from pain: (4) the respect for the freedom and the dignity of the human person, without discrimination; (5) an up-to-date scientific qualification (Art. 5). The authors underline that autonomy is an anthropological--and consequently ethical-- characteristic of the human person. Different positions on autonomy in bioethics (individualistic, evolutionistic, utilitarian and personalistic models) are explained. The relation between the professional autonomy of the physician and the autonomy of the patient and of colleagues is discussed. In fact, the medical doctor is obliged: (1) to respect the fundamental rights of the person, first of all his/her life; (2) to ensure the continuity of the care, even if he can only relieve the patient's suffering; (3) to maintain, except under certain circumstances, professional secrecy and confidentiality regarding patients and their medical records. Moreover, the physician cannot deny the patient correct and appropriate information. He/she should not perform any diagnostic or therapeutic activity without the informed consent of the patient and the medical doctor must give up medical treatment in case of documented refusal of the individual. Furthermore, the medical doctor has the right to raise conscientious objections if he/she is requested to perform medical actions that are contrary to his/her conscience or medical opinion, unless this attitude would seriously and immediately harm the patient. Regarding the relationships with colleagues, the physician is obliged to solidarity, mutual respect, and care of sick colleagues. Finally, the authors discuss the Italian legislation affecting the physician's professional autonomy: (1) the SSN health care Acts; (2) the so-called Charter for Public Health Care Services; (3) the Acts on privacy; (4) Good Clinical Practice.

[Cardiac rupture: a not infrequent complication of acute myocardial infarction. Report of five cases (author's transl)]. / La rottura di cuore: una non rara complicanza dell'infarto miocardico acuto. Descrizione di 5 casi.

Five cases of cardiac rupture (CR) in acute myocardial infarction (AMI) (four men and one woman aged between 49 and 86 years, mean 64) are described. The incidence of CR was 4,7% of 106 cases of AMI and 20,8% of causes of death. In all cases, pathologic observations well agreed with electrocardiographic site of infarction. All patients had ECG pattern of transmural AMI: postero-inferior (2 cases), anterior (1 case); none of them had myocardial infarction in the past. Two patients had systolic hypertension on admission, during and immediately before death, and 3 patients were normotensive during the whole course of illness. All patients had severe, prolonged and resistant to opiate therapy chest pain, which reexacerbated immediately before death in two cases. 4 patients died within 24 hours after the onset of symptoms. Terminal ECG pattern was similar in these four cases: sudden sinus bradycardia and/or idio-ventricular rhythm, with a progressive slowing of heart rate and changes of QRS patterns of "agonic" type, preceded electrical activity cessation. In one patient, who died at the seventh day of illness, ventricular fibrillation was observed. The AA. stress the importance of the early recognition of clinical findings suggesting an impeding CR in order to relieve cardiac tamponade with pericardiocentesis and to perform, as soon as possible, surgical treatment.

[The scimitar syndrome. A clinical contribution and review of the literature (author's transl)]. / La "sindrome della scimitarra." Contributo clinico e revisione della letteratura.

The scimitar syndrome groups a combination of several congenital anomalies in the right lung with an abnormal right pulmonary venous drainage in the inferior vena cava or the right atrium. After a survey of 130 cases in the literature, clinical, angiografic and hemodynimac features of the syndrome are defined. The Authors report two new cases diagnosed in adults, characterised by a clean discordance between the clinical features and the angiographic ones. The former case is completely asymptomatic and the radiographic feature is typical, while the latter shows a characteristic symptomatology but there isn't a clean "scimitar image". But notwithstanding the absence of this "scimitar image", the Authors think that the anomalous pulmonary drainage in the right atrium and the several anomalies in the right lung can be attributed to the scimitar syndrome, physiopatologically.

Effects of hospitalization on affective status of elderly patients.

The effects of hospitalization on affective status were assessed by an original protocol in 214 consecutive elderly patients (mean age = 78.3 +/-5.0 years, range = 70-92 years). Psychological decompensation was significantly related to length of stay (p less than 0.01) and drug use (p less than 0.05) and unaffected by sex, marital status, prior living place, diagnostic category. Affective status and functional status were directly correlated (p less than 0.0001), although in 51% of medical patients the affective status worsened or remained unchanged despite improved physical function. Improvement in affective status occurred more frequently in surgical patients (p less than 0.001) due to psychological improvement following surgery. Physicians providing medical and surgical care for geriatric patients must remain aware of the patients' emotional response to hospitalization and illness, given the accompanying risk for psychological decompensation.

[Benzodiazepines consumption and risk of dependence in institutionalized geriatric patients]. / Consumo di benzodiazepine e rischio di dipendenza in pazienti geriatrici istituzionalizzati.

The use of psychoactive drugs in geriatric nursing homes has to be considered within the peculiar frame work of the elderly condition. The present study was aimed at verifying the prevalence and characteristics of prolonged benzodiazepine use (greater than 1 month) in the entire elderly institutionalized population of an Italian region (Molise). In the 31 benzodiazepine consumers identified, psychosocial and clinical data were recorded by means of a specific scale and of a semistructured interview for the assessment of drug effects. The dependence potential was evaluated in a smaller sample of 18 patients, recording with a scale the onset of withdrawal and/or rebound symptoms following discontinuation of drug treatment. The characteristics of prescription appeared to be generally correct and no appreciable tendency toward abuse was evidenced. In only one patient, discontinuation of benzodiazepines precipitated a confusional state. In other 5 patients significant but not severe withdrawal symptoms were recorded. Duration of treatment was the only variable moderately correlated with the onset of withdrawal/rebound symptomatology (p less than 0.1). In conclusion, the results of our study are reassuring but they should not induce to disregard important clinical aspects of psychopharmacotherapy in the elderly, such as: psychopathological diagnosis, drug associations and interactions, duration of treatment and dosage of prescribed benzodiazepines.

Autopsy rate in younger and older hospitalized patients.

A retrospective study of the autopsy rate of the clinico-pathological correlations was made in a group of inpatients. The trend of autopsy rate was observed in all inpatients died in a university hospital during a nine year period (from 1975 to 1983). The agreement between the clinical and pathological death diagnosis was retrospectively controlled in 294 consecutive patients died and submitted to autopsy in the same hospital during a 6 month period (from January to June 1983). The results show that: In the oldest (greater than 60 yrs) patients, the autopsy rate trend was significantly reduced from 1975 to 1983, whereas the hospital admissions and the mortality rate increased. In the youngest subjects (less than 60 yrs), the autopsy rate trend, the hospital admissions and the mortality rate did not significantly change from 1975 to 1983. In all the years considered, the autopsy rate was significantly reduced in the oldest class (p less than 0.001). The agreement between the clinical and pathological diagnosis was observed in 83% of cases in the less than 60 years class and in 63% of cases in the greater than 60 yrs class (p less than 0.001). The association of main disease with other diseases was significantly more frequent in the greater than 60 yrs class with respect to the less than 60 yrs class (p less than 0.01). It has been concluded that the autopsy, especially in the elderly, is absolutely necessary for a better quality control of the clinical diagnosis and of the medical care.

Neuropeptide Y plasma levels and immunological changes during academic stress.

Academic stress is a good model of psychological stress in humans for studying psychoneuroimmune correlations. We looked for correlations between psychological scores, immune tests and plasma levels of cortisol and neuropeptide Y (NPY). A group of medical students were evaluated at the beginning of the academic year (Baseline) and the day before an examination (Stress). They underwent evaluation by The Profile of Mood States (POMS), The Malaise Inventory, The Self Efficacy Scale and A Global Assessment of Recent Stress (GARS). The lymphocyte subsets, the lymphocyte proliferative response and the cytokine production were also evaluated. We detected modifications of some psychological test scores between the Baseline and Stress evaluation, a significant reduction of lymphocyte proliferation, IL-2 production and percentage of the lymphocyte CD19, and an increase in plasma cortisol levels during stress. The lymphocyte proliferation negatively correlated with the POMS score as well as the percentage of CD16+ cells with NPY plasma levels. NPY levels were not different from Baseline. The emotional and mood states seem to influence immunity. Copyrightz1999S.KargerAG,Basel