Circadian rhythm of some parameters of body composition in the elderly investigated by means of bioelectrical impedance analysis.

We studied the within-day determinations of some body composition (BC) parameters in clinically healthy elderly subjects with the aim of investigating their circadian rhythms (CR), which are known to vary in a circadian manner in clinically healthy young adults. The study involved six non-smoking, clinically healthy elderly males (mean age: 75 +/- 4 years; mean weight: 71.07 +/- 10.26 kg; mean height: 170 +/- 5 cm, mean BMI: 24 +/- 1 kg/m2). The BC parameters were determined by means of bioelectrical impedance analysis (BIA) at 2-hour intervals during the day and night, with the subjects lying horizontally in bed. The time-qualified BC estimates were analysed using the Cosinor method. The analysis revealed that the healthy elderly subjects had lost the CR of a number of the BC parameters, including fat body mass, cell body mass, extracellular body mass, total body water, extracellular body water, intracellular body water, and the Na and K exchangeable pools. However, they still retained the CR of body weight and lean body mass, with the expected nocturnal phase of oscillation. The abolition of the CR of the majority of BC parameters in the elderly suggests that human senescence is characterised by consistent changes in the daily rhythmic patterns of fat, water and electrolyte metabolism.

Neural network analysis in predicting 2-year survival in elderly people: a new statistical-mathematical approach.

We designed this study to test the usefulness of artificial neural networks (ANN) in assessing 2-year survival in elderly persons, and to understand the net's logical functioning, thus determining the relative importance of the single biological and clinical variables which influence survival. ANN are statistical-mathematical tools able to determine the existence of a correlation between series of data and, once 'trained', to predict output data given input data. Although ANN have been applied in various areas of medical research, they have only very recently been applied in geriatrics (Cacciafesta et al., 2000. Arch. Gerontol. Geriatr. 31 (in press)). We built up an ANN to investigate how 17 clinical variables relating to a sample of 159 elderly people affect survival, and the possibility of predicting 2-year survival or non-survival for each single subject. When tested on a sample of 20 elderly people, the trained network gave the correct answer in 85% of the cases. We then extracted the mathematical function that the net used for calculating the output (survival) for each set of input data (clinical variables). Using this formula, we investigated how some clinical variables influence 2-year survival: we found that a low serum cholesterol level is an unfavourable characteristic in relation to survival. We conclude-despite the fact that the sample studied was relatively small-that ANN are useful in predicting 2-year survival in elderly people. The mathematical function we obtained from the net seems useful in determining the relative importance of single variables related to survival.

A neural network study of the correlation between metabolic-cardiovascular diseases and disability in elderly people.

Numerous studies have affirmed the existence of a correlation between various cardiovascular diseases and functional decline in elderly people. Not much information, however, is available concerning the overall effect of various, possibly coexisting, cardiovascular pathologies, or metabolic conditions notoriously related to them, on determining disability. We wanted to verify if it were possible to assess: (1) The overall importance of various metabolic and cardiovascular diseases which elderly people often suffer from contemporaneously in determining a condition of not self-sufficiency; (2) The possibility of predicting a condition of not self-sufficiency in relation to the above-mentioned pathologies. In order to achieve this aim, we used an artificial neural network: a statistical-mathematical tool able to determine the existence of a correlation between series of data and, once 'trained', to predict output data given the input data. Although artificial neural networks have been applied in various areas of medical research, they have not been previously applied in geriatrics. We have applied this method to a sample of 179 elderly people, demonstrating that seven clinical-biological variables concerning their metabolic and cardiovascular conditions are strictly related, all together, to the presence or otherwise of a functional impairment. When tested on a sample of 20 'unknown' elderly people, the trained network gave the correct answer-self-sufficiency or not self-sufficiency-in 95% of the cases. Despite the fact that the sample studied was relatively small, artificial neural networks are undoubtedly useful in predicting functional impairment in elderly people in relation to the presence of metabolic and cardiovascular diseases.

Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial.

The encouraging results of recent multicenter clinical trials conducted in the US on the effect of carvedilol therapy in patients with chronic heart failure, prompted us to verify its tolerability in a group of elderly patients. For the open, randomized, placebo-controlled study, we selected 40 patients (28 men and 12 women, mean age 76.8+/-5.9 years) with mild, moderate or severe chronic heart failure. Exclusion criteria included dementia, chronic hepatitis, renal failure, severe vascular disease and respiratory failure. All patients were receiving treatment with digitalis, furosemide and ACE inhibitors. The study lasted 12 weeks. During the first week, all subjects received oral placebo or carvedilol, at a dose of 6.25 mg twice daily. The twice daily dose was then increased to 12.5 mg during weeks 2-4 and to 25 mg from weeks 5-12. At 0, after the 2 weeks of run-in, 4 and 12 weeks patients underwent assessment of systolic and diastolic blood pressure, heart rate, left ventricular ejection fraction, cognitive status and functional ability. Our findings indicate that elderly patients with congestive heart failure tolerate carvedilol therapy well. Carvedilol slightly improves heart function without altering functional or cognitive ability. A larger-scale trial in geriatric patients is now required to determine whether this treatment will reduce serious morbidity or mortality from heart failure.

[The efficacy and tolerance of orally administered kallikrein in patients with essential arterial hypertension]. / Efficacia e tollerabilità della somministrazione orale di callicreina in pazienti affetti da ipertensione arteriosa essenziale.

Since the reduced kallikrein excretion demonstrated in essential hypertension suggested the possibility of an impairment in the renal kallikrein-kinin system, we decided to evaluate the efficacy and safety of oral kallikrein administration (glandular kallikrein derived from porcine pancreas) in 30 essential hypertensive subjects (21 males, 9 females, age range 34-62 years). Twenty subjects took 150 IU kallikrein t.i.d. for eight days; during this period their sodium intake remained normal (120 mEq Na+/die). Ten subjects took placebo. After the trial period, urinary kallikrein in the active group increased from 0.9 +/- 0.4 U/24 h (normal value greater than 1.2 U/24 h) to 1.6 +/- 1 U/24 h (p less than 0.05); systolic and diastolic blood pressure decreased respectively from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg (p less than 0.01) and from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg (p less than 0.025); urinary sodium and potassium excretion increased respectively from 96.7 +/- 17 mEq/24 h to 119.1 +/- 32.3 mEq/24 h (p less than 0.05) and from 36.7 +/- 11 mEq/24 h to 43.5 +/- 12.8 mEq/24 h (p less than 0.05). One patient in the kallikrein group suffered a transient episode of gastric pain. No modifications of the parameters evaluated were observed in the placebo group. We conclude that kallikrein has a mild hypotensive effect in hypertensive subjects and is generally well-tolerated. Its antihypertensive effect is probably due to the sodiuretic action of the substance.

[Nitrendipine: evaluation of the duration of the antihypertensive effect at different doses using the conventional method and ambulatory monitoring of arterial pressure]. / Nitrendipina: valutazione della durata dell'effetto antipertensivo a dosaggi differenti con il metodo convenzionale e con il monitoraggio ambulatoriale della pressione arteriosa.

To evaluate the effect-duration of nitrendipine in 20 moderate essential hypertensives (aged from 42 to 66, mean +/- SD: 55 +/- 7) when treated with 20 mg once or twice a day, we utilized the blood pressure standard method of measurement and the ambulatory monitoring. Blood pressure determinations were made during the follow-up at 2- week intervals for 3 months, each measurement being made with a mercury sphygmomanometer, 24 +/- 3 hours after the last dose; laboratory parameters, 2 24-hour blood pressure monitoring (ICR 5200, Spacelabs) and standard ECG were performed at baseline and after 3 months. Following a 2-week run-in period with placebo bid (at 10.00 am and 10.00 pm) a 20 mg morning dose of nitrendipine was started continuing the administration of the placebo tablet at 10.00 pm. The dosage was changed to a twice active daily regimen, with an increase in the daily dose (20 mg twice a day) in those patients whose diastolic blood pressure remained greater than 90 mmHg after a 4-week control. After the twelfth week, another 2-week placebo run-in followed the active treatment. Supine blood pressure recorded after 3-month therapy, showed a significant (p less than 0.0001) reduction in both systolic and diastolic mean values (22/15 mmHg) at the end of active treatment in the 16 patients who ended the trial. In particular, the responders to 20 mg (5 patients) showed a blood pressure reduction of 18 mmHg in comparison with the run-in period; in the other group of responders to increasing dosage of 40 mg (11 patients), we observed a 8 mmHg diastolic blood pressure reduction at 28 days and a successive 7 mmHg at the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of nicardipine in hypertensive patients with chronic kidney insufficiency]. / Effetti della nicardipina in pazienti ipertesi con insufficienza renale cronica.

There has been a increasing awareness that calcium antagonists may have beneficial effects on the kidney. Therefore we evaluated the renal and antihypertensive effects of nicardipine treatment in 12 hypertensive patients with chronic renal failure. The drug was given at a dose of 20 mg three times a day. Blood pressure was normalized in almost all cases while the indexes of renal function were improved. A transient deterioration of renal function, probably due to reduction of glomerular capillary pressure was observed in some cases. In conclusion, our data showed a beneficial effect on renal function during nicardipine therapy. This effect could be absent in the most advanced degree of renal damage.

Blood platelets and angiotensin II: angiotensin II release after platelet aggregation.

Recent studies have demonstrated the presence of angiotensin II (Ang II) in human platelets. The aim of the present study was to determine whether in vitro platelet aggregation induces Ang II release. We studied 20 healthy volunteers, and found that some aggregant stimuli can cause the platelet to release this peptide. Release of Ang II was greater with thrombin (40.7%) than with ADP (29%), while N-ethylmaleimide was almost ineffective. The release of Ang II following in vitro aggregant stimuli suggests that this may be one of the mechanisms through which platelets can locally modulate vascular tone and perhaps promote atherogenesis.

Effect of nicardipine on angiotensin II platelet content.

We evaluated the effect of nicardipine treatment on platelet angiotensin II content in 18 essential hypertensive patients. Nicardipine induced a decrease in platelet angiotensin II content in all patients (-14%), but particularly in 10 (P less than 0.05; -20.5%). No other differences were found between these patients and the others. Further investigations are required to determine whether platelet angiotensin II content reduction contributes to the prophylactic and therapeutic effects of calcium antagonists on atherosclerosis.

Effect of angiotensin converting enzyme inhibition on platelet angiotensin II content.

The effect of captopril treatment on platelet angiotensin II levels was evaluated in 12 patients with essential hypertension. Captopril significantly lowered (p less than 0.01) mean arterial blood pressure in seven patients (Group 1) and was ineffective in five (Group 2). In Group 1, a marked decrease in plasma angiotensin II levels in both the supine (from 5.5 +/- 0.5 to 2.8 +/- 0.9 pg/ml) and the upright positions (from 17.5 +/- 4.7 to 3.9 +/- 1.6 pg/ml; p less than 0.0025) and a significant increase in platelet angiotensin II levels (from 10.5 +/- 5.3 to 22.4 +/- 17 pg/ml; p less than 0.05) after captopril treatment was observed. In Group 2, no variation was found in plasma angiotensin II levels, whereas platelet angiotensin II levels increased slightly (from 10.8 +/- 3.1 pg/ml to 16.9 +/- 5.2 pg/ml; NS). These findings suggest that the decrease in plasma angiotensin II levels can lead to an increase in platelet angiotensin II receptors or can lead to angiotensin II production in platelets through activation of a feedback mechanism. The second hypothesis suggests that platelets have alternative enzymatic pathways leading to angiotensin II production not inhibited by captopril.

Relationship between vasopressin and the renin-angiotensin-aldosterone system in essential hypertension: effect of converting enzyme inhibitor on plasma vasopressin.

The effect of the chronic administration of captopril on plasma levels of vasopressin (PVP) were studied in 14 patients with moderate essential hypertension and 10 normal volunteers. All patients were studied after 10 days without drugs and under a constant diet (120 mmol sodium and 80 mmol potassium/day). Plasma levels of renin activity (PRA), aldosterone (PA) and PVP were assayed before and after captopril treatment (50-100 mg/day for 1 month). In addition to the well-known effect of captopril treatment on PRA and PA, a statistically significant reduction of PVP was observed. This finding suggests that the renin-angiotensin-aldosterone system influences vasopressin release, and its inhibitors may contribute to the absence of water retention during captopril treatment compared with the effect of other vasodilatory drugs.