[Acute and persistent antiproteinuric effect of a low-protein diet in chronic kidney disease]. / Acuto e persistente effetto antiproteinurico della dieta ipoproteica artificiale nella malattia renale cronica.

This study aimed to evaluate the anti-proteinuric effect of a very-low-protein diet supplemented with essential amino acids and keto analogs in patients with moderate to advanced chronic kidney disease and proteinuria already treated with both ACE inhibitors and angiotensin-receptor blockers. The study was a prospective randomized controlled cross-over trial comparing a very-low-protein diet (VLpD) and a low-protein diet (LpD). We enrolled 32 consecutive patients between June 2000 and June 2005. They were randomized to receive a VpLD (group A) or an LpD (group B) for 6 months; thereafter, patients of both groups were switched to the other diet (group A to LpD; group B to VpLD) for a further 6 months. Finally, all patients were randomized again within each group to receive either LpD or VLpD and were followed for another year. The VLpD group showed a significant reduction of urinary protein excretion during the diet period, with a nadir at the fourth month of treatment; the amount of urinary protein reduction was about 58%. Serum advanced glycation end products (AGE) significantly decreased in 10 patients (5 of group A, 5 of group B; -18% and -19%, respectively) during VLpD. Univariate analysis showed that proteinuria correlated indirectly with VpLD and directly with AGE. This study demonstrates that in patients with moderate to advanced chronic kidney disease and severe proteinuria, a VLpD reduces both proteinuria and serum AGE, even in the presence of complete inhibition of the renin-angiotensin system.

Intralipid infusion combined with propranolol administration has favorable metabolic effects in elderly malnourished cancer patients.

Previous studies have shown that an elevated basal metabolic rate (BMR) is present in elderly malnourished cancer patients. A possible dysfunction of the autonomic nervous system needs to be demonstrated. In aged weight-losing cancer patients (n = 40), aged non-weight-losing cancer patients (n = 30), and aged weight-losing noncancer patients (n = 18), the baseline BMR and heart rate variability were studied. Aged weight-losing cancer patients (n = 40) underwent bioimpedance analysis, ambulatory electrocardiographic monitoring with analysis of heart rate variability, and determination of the BMR. Then, the patients received infusion of Intralipid (Pharmacia, Uppsala, Sweden) without and with propranolol (6 days of 40 mg twice daily) administration. At baseline, a simple correlation between the BMR and the low-frequency component (LF) (r = .42, P < .006) and LF to high-frequency (HF) ratio (r = .51, P < .001) was found. After propranolol administration, the percent decline in the BMR was significantly correlated with the percent decline in the LF (r = .39, P < .01) and LF/HF ratio (r = .53, P < .001). The percent decline in the BMR was not correlated with the HF (r = .13, P < .34) or the plasma noradrenaline concentration (r = .21, P < .20) at any time. With regard to the BMR and substrate oxidation, 6-day propranolol administration plus Intralipid infusion produced the strongest decline in the BMR. This study demonstrates that autonomic nervous system dysfunction occurs and is responsible for the elevated BMR in elderly cancer patients, propranolol administration rectifies the autonomic dysfunction, and Intralipid infusion combined with propranolol administration is useful for enhancing the daily caloric intake without a strong increase in energy expenditure.

Metabolic changes in elderly cancer patients after glucose ingestion. The role of tumor necrosis factor-alpha.

BACKGROUND: Previous studies have demonstrated an increased basal metabolic rate in cancer patients. However, no previous study has investigated the changes in energy expenditure and substrate oxidation after administration of a glucose load. Furthermore, the role of tumor necrosis factor-alpha (TNF-alpha) on cancer-induced metabolic changes is still a neglected area. METHODS: In 25 cancer patients and 16 healthy subjects matched with regard to age, body mass index, and fat-free mass, indirect calorimetry was made before and after administration of a glucose load (75 g per subject, administered orally). RESULTS: Cancer patients had fasting plasma concentrations of insulin (74 +/- 3.3 vs. 67 +/- 4.1 pmol/L; P < 0.05), lactate (0.68 +/- 0.11 vs. 0.41 +/- 0.1 mmol/L; P < 0.05), free fatty acids (884 +/- 121 vs. 342 +/- 76 mmol/mL; P < 0.001), and TNF-alpha (1.23 +/- 0.31 vs. 0.45 +/- 0.11 ng/mL; P < 0.01) greater than controls, whereas plasma glucose concentrations (4.8 +/- 0.5 vs. 5.1 +/- 0.3 mmol/L; P = not significant) were not different from controls. Indirect calorimetry at baseline demonstrated that basal metabolic rate, fat oxidation, and protein oxidation were significantly greater in cancer patients than in controls. After administration of the glucose load, carbohydrate oxidation progressively rose in both cancer patients and controls, with no differences between the two groups, whereas glucose uptake (59.3 +/- 3.8 vs.69.1 +/- 3.6 g/kg fat-free mass [FFM] x 240 minutes; P < 0.01) and storage (49.1 +/- 4.1 vs. 60.2 +/- 3.3 g/kg FFM x 240 minutes; P < 0.05) were markedly reduced in cancer patients as compared with controls. Finally, glucose-induced thermogenesis (GIT) was lower in cancer patients than in controls. CONCLUSIONS: This study demonstrated that GIT is lower in cancer patients than in healthy subjects matched with regard to age and body mass index. An overactivity of the glucose fatty acid cycle is responsible for such results. Plasma concentrations of TNF-alpha might play a modulating role in the metabolic changes that occur after administration of a glucose load. The role of TNF-alpha on glucose and lipid metabolism in cancer patients would be a worthy subject of future investigations.

Regression of left ventricular hypertrophy in hypertensive elderly patients with carvedilol.

In hypertensive patients, the development of left ventricular hypertrophy seems to increase the risk of cardiovascular death although some antihypertensive agents have been associated with regression in left ventricular hypertrophy. A few studies have evaluated the carvedilol, a new drug having a balanced pharmacology of vasodilatation and beta-receptor blockade, particularly in elderly hypertensive patients. To test its effects on left ventricular hypertrophy, patients with essential hypertension and left ventricular hypertrophy were studied before and at the end of 6 months of therapy with 25 mg of carvedilol daily. Candidates had to have moderate, uncontrolled essential hypertension with echocardiographically documented left ventricular hypertrophy (left ventricular mass index > 130 g/m2 for men and > 110 g/m2 for women). Of 26 patients selected, 4 dropped out. The remaining 22 patients successfully completed 6 months of therapy. The average age was 69 +/- 8 years. Carvedilol caused a significant reduction of mean systolic blood pressure from 175 to 145 mmHg (p < 0.001), of diastolic blood pressure from 102 to 82 mmHg (p < 0.001), of left ventricular mass index from 148 +/- 24 g/m2 (p < 0.003), and a non significant change of the mean heart rate from 78 to 72 beats/min. In our study, carvedilol was well tolerated in patients with essential hypertension and left ventricular hypertrophy.

Clinical effects of oral theophylline in elderly patients with sick sinus syndrome.

Theophylline increases the heart rate in patients with normal sinus rhythm and in patients with sick sinus syndrome. This effect is probably connected to the blockade of adenosine receptors by theophylline. This study evaluated the efficacy of theophylline in 34 elderly patients with symptomatic sinus bradycardia (age 68 +/- 11 years). A resting electrocardiogram, a 24-hour recording and treadmill test were performed both before and after administration of slow-release theophylline (700 mg/day). The drug increased resting heart rate (from 43 +/- 6 to 63 +/- 16 beats/min, p < 0.01), mean 24 hour heart rate (from 49 +/- 7 to 65 +/- 17 beats/min, p < 0.01), and minimal 24 hour heart rate (from 34 +/- 5 to 44 +/- 10 beats/min, p < 0.05 ). Cardiac pauses longer than 2.5 seconds were present in 8 patients during control recordings, and disappeared after theophylline. Twenty-six patients were followed for a period of 20 +/- 5 months. Suppression of symptoms was achieved in 24 of them. Asthenia and easy fatigue were reduced markedly by the drug. During long term therapy, the sinus rate was similar to that observed at the steady-state evaluation. In 6 of the 34 patients theophylline had to be discontinued because of gastric intolerance (in 4 cases at the end of the steady-state evaluation and in 2 during long-term therapy). These data suggest that oral theophylline can represent an effective therapy in some elderly patients with symptomatic sinus bradycardia and can avoid or delay the need of a permanent pacemaker.

Isoproterenol test and head-up tilt test for diagnosis of vasovagal syncope in elderly patients.

The elderly can be affected by vasovagal syncope, but they often do not have preceding symptoms. The head-up tilt test (HTT) is successfully used in half of the patients in which the diagnosis is difficult. In young people the association with the isoproterenol test improves the sensitivity of the HTT. In the elderly the effect of such an association is still debated, therefore, the present study was aimed at evaluating the usefulness of the association between the two tests in old subjects to unmask the vasovagal nature of some syncopes of unknown origin. Twenty-four patients with negative HTT (18 males and 6 females; mean age 65 years) 10 with and 14 without organic heart disease were studied. The test protocol consisted of a continuous intravenous infusion of isoproterenol in successive stages starting from a dosage of 1 gamma/min for 5 min in supine position and then for 10 min in passive upright position at 80 (1st stage) up to maximum of 5 gamma/min (5th stage). The results obtained were: 12 patients (50%) had a positive test (reproduction of syncope) with a vasodepressor response in 6 of them and a mixed response in 6 patients. The mean time to syncope was during the 4th min of the 4th stage of treatment. The heart rate increase was 36% between the initial and peak values achieved during the test in patients with a positive test, and 10.5% in patients with negative test (p < 0.05). These results indicate that the isoproterenol test seems to increase the sensitivity of HTT in elderly patients with syncope of unknown origin.

The oncological therapy in the elderly.

The rising incidence of cancer in old subjects yields great scientific interest. Cancer itself has different features in the elderly. Thus the choice of therapy must follow a wide investigation on the "performance status" through acknowledgements on psychological and social factors, too. The therapeutic strategy is not usually different from the one used in other sections of life, but it is important to remember that an aged patient with cancer has to be submitted to a multidimensional evaluation using specific tools, that consider not only the neoplastic pathology but also the functional consequences. Always respecting quality of life and the eventual side effects, the choice of less aggressive strategies is especially important in those patients presenting a reduced expectancy of life. The improvement of surgery and anesthesiological techniques, the use of high-energy radiotherapy, the use of hemopoietic growing factors, antiemetics of last generation and a suitable support therapy give the medical specialist the chance to choose the adequate therapeutic strategy. This is a short review of the main guide-lines to be taken into consideration in the assessment and management of elderly patients with cancer.

Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects.

Our study investigates short- and long-term effects of infusion of non-esterified fatty acids (NEFA) on insulin secretion in healthy subjects. Twelve healthy individuals underwent a 24-h Intralipid (10% triglyceride emulsion) infusion at a rate of 0.4 ml/min with a simultaneous infusion of heparin (a bolus of 200 U followed by 0.2 U/min per kg body weight). After an overnight fast (baseline), at 6 and at 24 h of Intralipid infusion and 24 h after Intralipid discontinuation (recovery test), all subjects underwent an intravenous glucose tolerance test (iv-GTT) (25 g of glucose/min). Intralipid infusion caused a threefold rise in plasma NEFA concentrations with no difference between the 6- and the 24-h concentrations. Compared to baseline acute insulin response (AIR) (AIR = 63 +/- 8 mU/l), short-term (6-h) Intralipid infusion was associated with a significant increase in AIR (86 +/- 12 mU/l p < 0.01); in contrast, long-term (24-h) Intralipid delivery was associated with inhibition of AIR (31 +/- 5 mU/l) compared to baseline (p < 0.001) and to the 6-h (p < 0.03) triglyceride emulsion infusion. Intralipid infusion was associated with a progressive and significant decline in respiratory quotient (RQ). A positive correlation between changes in fasting plasma NEFA concentrations and AIR at the 6-h infusion (r = 0.89 p < 0.001) was found. In contrast, at the end of the Intralipid infusion period, changes in plasma NEFA concentrations and AIR were negatively correlated (r = -0.87 p < 0.001). The recovery test showed that fasting plasma NEFA concentrations, RQ and AIR had returned to baseline values. In the control study (n = 8) 0.9% NaCl infusion did not mimick the effect of Intralipid. In conclusion, our study demonstrates that short- and long-term exposures of beta cells to high plasma NEFA concentrations have opposite effects on glucose-induced insulin secretion.

Lisinopril administration improves insulin action in aged patients with hypertension.

Thirty elderly, mildly hypertensive patients were enrolled for a single-blind, randomised cross-over placebo controlled trial in which placebo and lisinopril (20 mg/day before breakfast) were given for 4 and 8 weeks, respectively. A wash-out period of 3 weeks between placebo and lisinopril was observed. In each patient a euglycaemic glucose clamp with simultaneous indirect calorimetry allowed us to determine whole body glucose disposal and substrate oxidation. Changes in morning SBP and DBP were also determined. Lisinopril vs. placebo significantly improved whole body glucose disposal (40.4 +/- 0.4 vs. 30.3 +/- 0.4 mumol/kg LBM x min; P < 0.01), non-oxidative glucose metabolism (18.1 +/- 0.7 vs. 10.9 +/- 0.6 mumol/kg LBM x min; P < 0.01) and fasting plasma potassium levels (4.8 +/- 3 vs. 4.4 +/- 0.4 mmol/l; P < 0.05). SBP (175 +/- 3.3 vs. 160 +/- 3.0 mm Hg; P < 0.001) and DBP (106 +/- 2.3 vs. 95 +/- 2.0 mm Hg; P < 0.001) were significantly reduced by lisinopril administration. After ACE inhibition, fasting plasma potassium levels correlated with the decline in mean arterial BP (r = -0.71; P < 0.006). In conclusion, lisinopril administration reduces arterial BP and improves insulin sensitivity in elderly hypertensive patients.