Pharmacotherapy in the extreme longevity.

The increased longevity brings to the appearance of more polypathologies, being frequently of chronic-degenerative type, and also an increased use of pharmaca. The present study evaluated the usual drug consumption in the ultralongevous people in comparison with their clinical conditions. A total of 602 centenarians were involved: clinical anamnesis, objective examinations and clinico-functional evaluations were performed. In 555 of them an acceptable pharmacological anamnesis was obtained. The results showed that 28 centenarians (5%) did not take any drug, 527 (95%) of them used regularly some pharmacological therapy. Their distribution was: 1 drug/day 68 (13%), 2 drugs/day 86 (16.3%), 3 drugs/day 344 (65.2%), more than 3 drugs/day 29 (5.5%). The mean daily drug consumption was 2.7+/-1.4. Good clinical conditions could be established in 115 (20.7%) of the centenarians, of them 28 subjects (24.3%) had used no drugs, 87 (75.7%) of them used 1-3 drugs/day. It was an important observation that adverse drug events (ADE) occurred in 15.2%. The ADE occurs frequently also in polypharmacological treatments, with various pharmacodynamic and pharmaco-kinetic modifications of the drugs. The mean daily drug consumption of the ultralongevous subjects was lower than that of the common elderly. This may be due to the past life of our centenarians, characterized by satisfactory health conditions, and also to a higher attention of the general practitioners in the drug prescriptions, as well as of the family members who administer the pharmaca.

C4, BF, C3 allele distribution and complement activity in healthy aged people and centenarians.

The aim of this study was to examine the complement system and the distribution of some human leukocyte antigen (HLA) class III alleles (C4, BF) in healthy aged people (77 centenarians and 89 elderly subjects). We have also studied the alleles of C3, a complement component genetically unrelated to HLA, the immunochemical levels of C4 and C3 and serum functional hemolytic activity for classical (CH50) and alternative (AP50) complement pathway. The levels of C3 and C4 and the CH50 and AP50 were found to be within the normal range. The frequencies of C3, BF, and C4A alleles were similar in the cohorts that have been studied. For C4B null allele (C4BQ0) a trend toward an increase in the older cohort was observed, although the differences were not significant after statistical correction. Our data suggest that the complement system is well preserved in centenarians and elderly subjects and class III HLA antigens are equally distributed in aged cohorts and in young healthy individuals.

Lipoprotein profile and high-density lipoproteins: subfractions distribution in centenarians.

In order to assess the role of HDL on longevity, we studied HDL subfraction distribution in centenarian women compared with a group of weight- and gender-matched healthy normolipidemic controls. We did not find any significant difference in the mean plasma lipid, apolipoprotein, and Lp(a) levels. On the contrary, in spite of similar HDL-cholesterol concentrations (1.32 +/- 0.41 mmol/l in centenarians vs. 1.32 +/- 0.25 mmol/l in controls, p = not significant), HDL2b and HDL3a levels were, respectively, significantly increased and significantly reduced in centenarians in comparison with controls (HDL2b 32.4 +/- 9.2% in centenarians vs. 23.4 +/- 7.7% in controls, p < 0.002, and HDL3a 26.3 +/- 9.8% in centenarians vs. 34.1 +/- 7.3% in controls, p < 0.01). Moreover, HDL2b levels were significantly raised and HDL3a levels were significantly reduced in centenarians in comparison with both 'middle-aged' and 'elderly' subjects, whereas no difference for any HDL subfraction was found between the two groups of controls of different ages. Age was significantly correlated with HDL2b and HDL3a (respectively, +0.452, p < 0.001, and -0.370, p < 0.01) in all subjects, but not with all the other lipid, lipoprotein and apolipoprotein parameters, but we observed a large overlapping of individual values of HDL2b between centenarians and controls. Since HDL2b levels were found to be inversely correlated with coronary heart disease risk, we could speculate that, in some cases, this may probably favor a healthy ageing, but long-term longitudinal studies are necessary to define the relative importance of HDL subfractions distribution as a marker of longevity. Probably other factors or clinical characteristics play a major role in the ageing process.

Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians.

In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.

Twelve-lead electrocardiographic analysis and pharmacotherapy in centenarians.

The prevalence of electrocardiographic anomalies has been assessed in a selected group of centenarians recruited in Western Sicily (49 subjects, 15 males and 34 females) with an average age of 101.5 years (range 100-109); the findings were analyzed in correlation with the state of health of the subjects, the drugs used and the presence of specific heart diseases and immobility. These subjects have rare signs of heart diseases, they do not show any electrolytic disorder, in spite of using many drugs sometimes in an inconsistent way. Particularly interesting is to note the moderate prevalence of sinus rhythm and the extremely low number of subjects with sinus respiratory arrhythmia as compared to the known literary data for the over-sixties. There occur, however, frequent, but almost asymptomatic troubles of the intraventricular conduction, especially left anterior hemiblock and ectopic beats. Atrial fibrillation and bradyarrhythmias are rare, while left axis deviation with scarce signs of left ventricular hypertrophy and alterations of the repolarization phase are frequent. The most used drugs are digitalis and vasodilators, especially angiotensin converting enzyme (ACE) inhibitors. The observed data prove that heart functions of the centenarians are in good conditions; the alterations of them are less serious than those of the somewhat younger old age classes, where the electrocardiographic anomalies are of higher extent and severity.

Plasma lipid, apolipoprotein and Lp(a) levels in elderly normolipidemic women: relationships with coronary heart disease and longevity.

The relation between plasma lipids and coronary heart disease (CHD) in the elderly is still debated, as well as the proposed role of lipoproteins as markers of longevity. In this study both normolipidemic elderly and middle-aged women with CHD showed higher triglycerides and apolipoprotein B levels and lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels in comparison with age-matched subjects without CHD. In the middle-aged group, hypertension and HDL-cholesterol levels and, in the elderly group, only HDL-cholesterol levels were independently associated with CHD. No significant difference was found between a group of healthy centenarians and elderly and middle-aged subjects without CHD. These data suggest that plasma lipids are also related to CHD in the elderly and that, even if at present we are not able to consider them as predictors of longevity, some lipoprotein features may contribute to select subgroups of subjects in which other factors play a further role in life expectancy.

[Chronic renal insufficiency of single kidney associated with genital, bone, and palpebral malformations]. / Insufficienza renale cronica da rene unico pelvico associato a malformazioni genitali, ossee e palpebrali.

Authors describe renal failure in a young woman with solitary pelvic kidney. Renal malformation was associated with genital and bone malformations that can be accounted for by the close relationship linking the genito-urinary and vertebral apparatuses during the first weeks of intrauterine life. Palpebral malformation which occurs very rarely in cases with renal malformations as reported in the literature was ascribed to hereditary factors. Changes of some indexes (serum and urine electrolytes, plasma renin and aldosterone) observed during the evolution of renal failure appear to confirm the role played by potassium in hormone balance and suggest repeated tests and dietary adjustments.

[A case of Martorell's ulcer: considerations on the use of hyperbaric oxygenotherapy]. / Sobre un caso de ulcera de Martorell: consideraciones sobre el empleo de la oxigenoterapia hiperbárica.

A case of hypertensive ulcer of martorell in a diabetic patient is described standing out the fast cure by means of Hyperbaric oxygenotherapy.

[Influence of high environmental temperature on various parameters of blood coagulation in healthy subjects and in thrombosis risk patients]. / Influenza dell'elevata temperatura ambientale su alcuni parametri della coagulazione in soggetti sani ed in pazienti a rischio trombotico.

The effects of environmental hyperthermia (exposure to a hot, dry microclimate) on the human body were investigated with particular reference to certain clotting parameters in healthy subjects and patients at risk of thrombosis. The study covered 70 volunteers, 10 of them clinically healthy (6 males and 4 females) aged 37.7 +/- 9.7 and 60 patients at risk of thrombosis aged 18-60 and divided according to pathology as follows: 26 with ischaemic cardiopathy, 22 with metabolic disorders (12 diabetics, 8 with dyslipidaemia, 2 with hyperuricaemia) and 12 with obliterating arteriopathies of the lower extremities (Fontaine stage 2 and 3). The following standardised protocol was adopted: 2 hours exposure in a controlled climate chamber (40 degrees C, 40-50% humidity, standard air speed 4 m/min, barometric pressure 760 mmHg) for a total of 8 exposures (2 per week for 1 month). This approach was adopted in order to assess not only the effect of each single exposure but also the role of any adaptation to heat. Three blood samples were taken from each subject for each session: the first in basal conditions in a comfortable environment, the second at the end of the 2 hour exposure; the third 30 minutes after the end of the session. Simultaneously samples of arterial blood were taken for pH assays and a spleen echography was performed in basal conditions and at the end of the session for each subject. Each blood sample was tested for several parameters essentially attributable to blood concentration for a broader view of the biological effects of exposure to heart (Ht, blood protein, Nat, K+). The clotting factors under specific study were also assessed (platelet count and volume, beta-thromboglobulin, PF4, von Willebrand Factor VIII, thromboxane B2, fibronectin). Body weight, blood pressure and oral temperature were also measured in all subjects before and after each session. In all subjects both healthy and at risk of thrombosis oral temperature increased (1 +/- 0.4 degrees); on average blood pressure was already higher in basal conditions in the patient group; body weight fell by 900 +/- 120 G in both groups. Ht and blood protein increased significantly in both groups while electrolyte changes were insignificant and blood pH showed a tendency towards acidosis. Clotting parameters revealed a tendency towards thrombophilia in all subjects: platelet count and volume were already higher in the patient group in basal conditions and increased after exposure to hyperthermia. Beta-thromboglobulin, FP4, Factor VIII, thromboxane B2 and fibronectin all increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of gastric acid secretion on interdigestive gastric motor activity and serum motilin in the elderly.

The purpose of this study is to investigate the influence of gastric secretion on the interdigestive gastric motor activity and related serum motilin variations in elderly subjects. The study was carried out on two groups of elderly subjects: one with achlorhydria or marked hypochlorhydria due to chronic atrophic gastritis and the other with normal acid secretion. A group of nonelderly subjects with normal acid secretion was also examined as control. Gastric motility was studied manometrically and serum motilin was measured by radioimmunoassay on blood samples taken every 15 min during the entire motor recording period of 200-300 min. Both groups of elderly subjects showed (1) alterations in interdigestive gastric motility and (2) serum motilin which was steadily high without the normal cyclic fluctuations. These studies suggest that the alterations in gastric motor activity and serum motilin in aged subjects are not related to the acid secretory capacity of the stomach. Other factors, such as alterations in the neurohormonal control system of gut motility, should be considered in the genesis of these age-related disorders.

Interdigestive plasma motilin concentrations in aged adults.

The interdigestive plasma motilin concentrations were evaluated in 13 over-65 healthy adults with no evidence of significant disease and in 19 younger individuals. Plasma motilin levels were determined every 15 min during a 3-hr fasting period, using a radioimmunological method. The individual median values of plasma motilin concentrations during the entire study period were significantly higher in aged than younger adults. The individual median coefficients of variation of motilin concentrations and the percentage increases of plasma motilin above baseline at each peak were significantly lower in the aged than in the young group. The results of this study indicate that during the interdigestive period aged individuals have markedly elevated circulating motilin levels, with less pronounced fluctuations than younger persons. This particular hormone pattern could be involved in motor disturbances of the stomach in elderly adults.

[A case of voluminous serous cystadenoma of the ovary. Clinico-social considerations]. / Su un caso di voluminoso cistoadenoma sieroso dell'ovaio. Considerazioni clinico-sociali.

The case of a voluminous serous cystadenoma of the ovary in a young woman is reported. At a time when health education and diagnostic progress have significantly modified the evolution of such neoplastic growths, the remarkable size of the tumour (28 litres of serous liquid), the absence of any complications whatsoever and the youth of the patient make the case particularly interesting and trigger a number of remarks on social factors.

[Ischemic syndrome of the lower extremities from immersion in hot water]. / Sindrome ischemica degli arti inferiori da immersione in acqua calda.

The present paper deals with an ischaemic syndrome which may affect an area of lower limb vessels with latent arteriopathy if limbs or whole body are immersed in very warm water. Two cases are described in which ischaemia appeared when the limbs involved were immersed in warm water (38 degrees C). Ischaemia may be explained by the occurrence of both haemometakinesia and insufficient reserve blood flow in the limbs involved. Aged patients are particularly prone to such syndrome due to the particular anatomic features of the vascular system in old age.

Serum potassium levels, red-blood-cell potassium and alterations of the repolarization phase of electrocardiography in old subjects.

Seventeen elderly patients are described, who showed minor changes in the e.c.g. recovery phase. Serum potassium levels appeared to be normal, but red-blood-cell potassium was found to be more or less markedly reduced. Restoration of the latter to normal values, which followed treatment with potassium salts was also associated with normalization of the e.c.g. pattern. These observations demonstrate that electrolyte disorders, and particularly hypokalaemia, may determine 'minor' alterations of repolarization much more frequently than is usually thought, and that determination of serum potassium levels is not a reliable tool for detecting potassium depletion, which is more accurately reflected by red-blood-cell potassium concentration.