D. Maugeri

Immunosenescence: a review.

Aging involves the morphological and functional integrity of all organs, including the cellular and humoral immunological functions. The main alterations can be listed as follows: (i) Thymic involution resulting in the decreased number of lymphoid precursor T- and B-cells. (ii) Reduced proliferative capacity of T-cells; loss of lymphocyte subgroups as a consequence of the shortening of telomeres. (iii) Qualitative deficiency of B-lymphocytes with a reduced response to exogenous antigens. (iv) Compromised activity of the accessory cells, both directly by depressing the chemotactic and phagocytic responses, and indirectly by increasing the prostaglandin production which inhibit the proliferation of T-cells. (v) Alterations in the production and secretion of various cytokines. (vi) Other factors like the general physiological conditions, the nutritional state, psychological habit and various hormone levels.

Glioblastoma in elderly patients: Safety and efficacy of adjuvant radiotherapy with concomitant temozolomide

The aim of this study was to evaluate the impact of radiotherapy plus concomitant and adjuvant temozolomide (TMZ), in terms of feasibility and activity, in elderly patients with glioblastoma. From January 2002 to December 2007, 42 consecutive patients with glioblastoma (27 men and 15 women) aged 65 years or more (median age 71.3 years), received radiotherapy plus concomitant and adjuvant TMZ. Nineteen patients (45.2%) had a Karnofsky index >or=80. Thirty-six patients (85.8%) underwent complete or subtotal resection, while 6 patients (14.2%) were only biopsied. All patients received adjuvant radiotherapy within 4 weeks from surgery. Twenty-two patients (54.8%) underwent adjuvant TMZ. Early discontinuation of concomitant TMZ program due to toxicity was observed in 8 patients. Considered variables were: age, Karnofsky index, surgery versus no surgery, radiation dose, and chemotherapy. At a median follow-up of 10.2 months, the 6- and 12-month overall survival rates were 81.9% and 27.8%, respectively. There was a significantly better survival for patients with a performance status according to Karnofsky >80 (p<0.0001). Actuarial progression-free survival at 6- and 12-month was 46.4% and 9.8%, respectively. Globally, the treatment was well tolerated with no treatment-related toxicity in 69% of patients. In conclusion, in elderly patients, the adjuvant chemo-radiotherapy was well tolerated with an acceptable rate of toxicity, and patients with a good performance status had a significantly better survival. However, further prospective trials are needed to confirm these results.

Adjuvant radiotherapy on older and oldest elderly rectal cancer patients

The purpose of this study was to evaluate the impact of radiotherapy in terms of feasibility and activity in the patients aged > or = 75 with advanced rectal cancer. From January 2002 to December 2006, 41 consecutive patients (27 men and 14 women) aged > or = 75 received radiotherapy for local advanced rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen patients received concomitant chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery versus no surgery, and timing of radiotherapy. The median age was 80.5 years (range 75-90). A total of 19.5% of the patients had no co-morbidity, 48.8% mild, 17.1% moderate, and 14.6% had severe co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All patients but one completed the planned radiation schedule. At a median follow-up of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 61.6%, respectively. There was a better survival for patients with no or mild co-morbidities (p=0.002) and a good performance status (p=0.003). The cancer-free survival at 2 and 4 years was 78.9% and 26.4%, respectively. No difference in acute and late toxicity rates was found between patients with different ACE-27 indexes. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

Laboratory parameters in centenarians of Italian ancestry

Studies aimed at collecting reference parameters for haematochemical analysis in the elderly are scarce and for the oldest old subjects even more rare. In order to establish the reference values for the most common laboratory text in long living individuals, we measured haematochemical parameters in >100 years old subjects and in aged subjects as control. Six hundred and two centenarians accepted to be enrolled in the study. A case history containing the complete anamnesis, clinical examinations, evaluation of the clinical cognitive and functional tests, was prepared for each centenarian. Blood samples from 120>100 years old subjects free of chronic or acute Illness (i.e. Alzheimers disease, metabolic diseases, cardiovascular disease, stroke, neoplastic and infectious diseases) were analysed. A population of 381 healthy old subjects (age range 65-85 years old), recruited in the same geographic areas and with the same clinical characteristic of the health centenarians, was utilized as control. Significant differences were observed for blood glucose, ALT, cholesterol and platelet levels, reduced in centenarians respect to the old subjects, whereas blood urea nitrogen levels were found significantly increased in centenarians. In conclusion, reference values of the healthy adults can generally been utilized also for the healthy oldest old group, with the notable exception of the above mentioned laboratory parameters that appear to be modified in long living subjects.

The comorbidities of elderly oncologic patients

The scope of this study was to evaluate the prevalence of comorbidity in elderly subjects with neoplastic diseases, and to compare it to those without tumor pathologies. Three groups of patients have been considered: (A)35 elderly oncological patients; (B)38 young/adult oncological patients; (C)25 elderly patients without oncological pathology. After clinical evaluation and pathohistological diagnostic analysis, the concomitant pathologies have been estimated by means of two methods: (i)the Satarianos score; and (ii)the Charlson Comorbidity Index (CCI). Statistical analyses performed by using the Chi-square and the Students t-test gave coherent results, and revealed that the prevalence of comorbidities was the highest in Group C, and displayed significantly reduced prevalences in the sequence Group B, Group A.

Alterations of the lymphocytic set-up in elderly patients with cancer

It is assumed that the increased incidence of neoplastic pathologies with advancing age is correlated with the immunosenescence and with the altered immune-surveillance. The present study was aimed at evaluating the role of the immunocompetent system and immunosenescence in carcinogenesis. A pool of 99 subjects (38 females, 61 males) has been analyzed in three groups as follows. Group A: 51 elderly subjects with cancer (16 females and 35 males, average age 73.7 +/- 7.5 years). Group B: 24 young subjects with cancer (12 females, 12 males, average age 49.5 +/- 10.3 years). Group C: 24 elderly subjects without any clinical evidence of cancer (10 females, 14 males, average age 74.6 +/- 6.3 years). Hemo-chromocytometric analysis and cytofluorimetric typifying have been performed in all subjects. A decrease of T (CD3+)-lymphocytes has been observed in group A, if compared to group B (P < 0.007), and to group C (P < 0.01), The T (CD4+)-lymphocytes were fewer in group A, than in group C (P < 0.004), and also the NK cells showed the same trend (P < 0.002). The numbers of leukocytes and monocytes increased in group A compared to group C (P < 0.01 and P < 0.004, respectively). Red cell numbers, hemoglobin and hematocrit values were lower in group A than in group B (P < 0.03, P < 0.03, P < 0.01, respectively), and also than in group C (P < 0.007, P < 0.001, P < 0.01, respectively), The results demonstrate that the alterations of the immunocompetent cells, particularly of the T-cell pool, may play an important role in the carcinogenesis of the elderly.

Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis

The use of Alendronate for the treatment of senile diabetes with osteopenia or osteoporosis is a common practice today, although the reasons for the success of this treatment are not completely understood. We investigated 40 elderly female patients, over 70 years of age, divided in two Groups (A and B) 20 cases of each, with insulin-dependent senile diabetes and fair metabolic balance, with an average disease duration of 30 +/- 4 years. They all had osteoporosis shown by the mean T-score of bone mineral densitometry. The Groups were treated as follows, Group A with 10 mg/day of Alendronate per os, with morning fasting plus a supplementation of calcium and vitamin D3, while the Group B received only calcium and vitamin D3 per os. Bone mineral density (BMD) expressed in mg/cm2, and in terms of T-score and Z-score at the spine (L1-L4) was monitored over time after 12 and 24 months, using dexa technique with a Lunar DPX densitometer. Moreover, the variation of daily consumption of insulin (DCI) of all the study population was calculated 12 and 24 months after the start of treatments. The data of Group A showed an improvement of osteoporosis, as evidenced by the increase of BMD at both times of measurement, accompanied by a significant reduction in the DCI (-21.6% by the 12th month, and -36.2% by the end of the observation period). In the Group B only small, statistically insignificant changes were observed in both the BMD and DCI. The most plausible explanation of reduction of DCI in Group A seems to be that Alendronate has improved the clinical symptoms of osteoporosis (pain, rigidity, and reduction of movements) through its action on the bone mass recovery and slowing down the bone turnover and under these conditions the diabetic patients improved their own physical performance. The better and more extensive movements certainly produced a reduction in the DCI, since a correct and adequate physical activity does contribute to an improved glucose metabolism.

Cytokine serum profile in a group of Sicilian Nonagenarians

The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-γ) and IL-2 levels are unmodified, suggesting a substantial maintenance of relevant T cell functions. In addition, a significant increase of IL-12 serum levels in nonagenarians versus young controls that might be related to the increase of natural killer (NK) cell functions characterizing aging processes was observed. The analysis of Th2 cytokines show an increase of IL-13 and a reduction of IL-4 levels mirroring the maintenance of some effectors mechanisms of the immunoresponse in advanced ages. Our results suggest that the multiplex analysis of cytokine levels might be useful in defining a successful aging profile.

Treatment of familial hypertriglyceridaemia with acarbose.

Aim: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega‐3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal α glucoside‐hydrolase. We evaluated the efficacy and side‐effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non‐diabetic patients.

The leptin, a new hormone of adipose tissue: clinical findings and perspectives in geriatrics

Obesity has gained a great importance during the last decades, and this fact stimulated numerous studies regarding the genetic causes of this disease. A recently discovered new molecule, called leptin, raised a wide interest. It is a product of the adipocytes, it exerts inhibitory effects on the center of appetite and increases the energy expenditure of the organism. The present study evaluated blood leptin levels in 57 elderly subjects and searched for eventual correlations between this parameter and the age, the body mass index (BMI), the fat body mass (fat%), the waist (W) and hip (H) circumference, as well as the ratio (R) of these latter two values (WHR). Blood leptin levels do not correlate with age, body height and the WHR, but display significant positive correlations with the body weight, the BMI, the fat%, the W, H and WHR. A deeper knowledge on leptin and the correlations of this hormone with other body parameters might be helpful in a better understanding of several pathogenetic mechanisms related to aging and involved in a deterioration of the quality of life in elderly, like multiple atherosclerotic and metabolic diseases (diabetes, dyslipidemias).