Giliola Calori

Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy

BACKGROUNDnTrimetazidine (TMZ) has been shown to partially inhibit free fatty acid oxidation by shifting substrate utilization from fatty acid to glucose. The aim of this study was to assess the effects of TMZ in patients with diabetes and ischemic cardiomyopathy.nnnMETHODSnSixteen patients with diabetes and ischemic hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days, and then again to receive either placebo or TMZ for 2 additional 6-month periods, according to a double-blind, crossover design. At the end of each period, all patients underwent exercise testing, 2-dimensional echocardiography, and hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value (index of total body glucose disposal) and endothelin-1 levels were evaluated.nnnRESULTSnBoth in the short and long term (completed by 13 patients), on TMZ compared to placebo, ejection fraction (47 +/- 7 vs 41 +/- 9 and 45 +/- 8 vs 36 +/- 8%, P <.001 for both) and M value (4.0 +/- 1.8 vs 3.3 +/- 1.6, P =.003, and 3.5 +/- 1.5 vs 2.7 +/- 1.6 mg/kg body weight/min, P <.01) increased, while fasting blood glucose (121 +/- 30 vs 136 +/- 40, P =.02 and 125 +/- 36 vs 140 +/- 43, P =.19) and endothelin-1 (8.8 +/- 3.8 vs 10.9 +/- 3.8, P <.001 and 6.2 +/- 2.4 vs 9.2 +/- 4.3 pg/mL, P =.03) decreased. In the short term, 10 patients decreased 1 class on the NYHA scale during treatment with TMZ (P =.019 vs placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment, while on placebo 1 patient increased 1 NYHA class and none improved (P =.018 vs placebo).nnnCONCLUSIONSnIn a short series of patients with diabetes and ischemic cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose metabolism, and endothelial function. Shifting energy substrate preference away from fatty acid metabolism and toward glucose metabolism by TMZ appears an effective adjunctive treatment in patients with diabetes with postischemic cardiomyopathy.

Acute effects of heparin administration on the ischemic threshold of patients with coronary artery disease: Evaluation of the protective role of the metabolic modulator trimetazidine

OBJECTIVESnWe sought to assess the effects of heparin and the potential protective effects of trimetazidine (TMZ) on exercise performance, plasma nitric oxide (NO), endothelin-1 (ET-1) and free fatty acid (FFA) release in patients with stable coronary artery disease (CAD).nnnBACKGROUNDnHeparin has been shown to reduce the ischemic threshold in patients with CAD. Trimetazidine may affect myocardial substrate utilization by shifting energy production from FFA to glucose oxidation.nnnMETHODSnIn four consecutive days, nine patients with CAD each received one of the following four regimens: 1) one tablet of placebo the evening before and at 8 AM and 4 PM on the day of the study, 10 ml of saline in a bolus 10 min before exercise, followed by an infusion of the same preparation; 2) placebo at the same times as in the first regimen, 5,000 IU of heparin 10 min before exercise, followed by 1,000 IU/h; 3) 20 mg TMZ at the same times as in the first regimen, 5,000 IU of heparin 10 min before exercise, followed by 1,000 IU/h; or 4) TMZ at the same times as in the first regimen, 10 ml of saline 10 min before exercise, followed by an infusion of the same preparation.nnnRESULTSnDuring placebo (test 2), heparin reduced the time to 1-mm ST-segment depression and prolonged the recovery time, as compared with the results of test 1. When heparin was administered after TMZ (test 3), the time to 1-mm ST-segment depression and the recovery time were similar to those recorded during saline (test 1). Finally, compared with all study phases, TMZ during saline (test 4) prolonged the time to 1 mm. No changes in NO release were found, whereas ET-1 was decreased at peak exercise and during recovery, when the patients were receiving TMZ (tests 3 and 4). Free fatty acids increased after heparin, both with placebo and TMZ.nnnCONCLUSIONSnIn patients with CAD, heparin reduces the ischemic threshold. Trimetazidine reduces the effects of heparin, probably by inhibiting FFA oxidation and enhancing glucose metabolism. The concomitant novel observation of reduced ET-1 release is likely to be also dependent on TMZ-induced improvement of endothelial metabolism or reduction of myocardial ischemia.

Genital plus audiovisual sexual stimulation following intracavernous vasoactive injection versus re-dosing for erectile dysfunction - Results of a prospective study

PURPOSEnWe assessed whether re-dosing of a vasoactive agent or the combination of a vasoactive injection and genital plus audiovisual sexual stimulation caused the greatest erectile effect to determine which of the 2 procedures would be better for dynamic penile color Doppler sonography in patients with erectile dysfunction.nnnMATERIALS AND METHODSnA total of 20 consecutive patients with erectile dysfunction underwent 2 sessions under real-time RigiScan* recording of penile erection. Session 1 consisted of adaptation in 10 minutes, intracavernous injection of 10 micrograms. alprostadil in 10 minutes and re-dosing of 10 micrograms. alprostadil in 10 minutes. Session 2 consisted of adaptation in 10 minutes, injection of 10 micrograms. alprostadil in 10 minutes and genital plus audiovisual sexual stimulation in 10 minutes. The total duration of each session was 30 minutes. The order of the 2 sessions was randomly assigned with a week interval between each session.nnnRESULTSnRe-dosing and genital plus audiovisual sexual stimulation caused a significant increase in erectile response compared to the result seen after the first injection (re-dosing p < 0.05, injection plus stimulation p < 0.01). However, erectile response after the genital stimulation session was significantly greater than that after re-dosing (p < 0.01). An erection comparable to the greatest spontaneous erection reported by the patient was much more frequently achieved after genital stimulation than after the re-dosing session (p < 0.01).nnnCONCLUSIONSnThe combination of injection and stimulation caused a significantly greater erectile response than re-dosing. We suggest that the former should always be used during color Doppler sonography to optimize the accuracy of the test. Re-dosing is suggested when an incomplete erectile response occurs after the injection plus stimulation phase.

Percent of Free Serum Prostate-Specific Antigen and Histological Findings in Patients Undergoing Open Prostatectomy for Benign Prostatic Hyperplasia

Purpose: To determine which pathologic features of the surgical specimen in men undergoing open prostatectomy for benign prostatic hyperplasia (BPH) correlate with preoperative and postoperative total, free prostate-specific antigen (PSA) levels and the free-to-total PSA ratio. Methods: Forty-four patients, undergoing open prostatectomy for BPH without evidence of prostate cancer in systematic biopsies and clinical prostatitis, were included in this prospective study. Each prostatectomy specimen was weighed and each slide was evaluated for inflammation (acute prostatitis, chronic-active prostatitis and chronic-inactive prostatitis), prostatic intraepithelial neoplasia, transitional/squamous metaplasia, cystic ductal dilation, leiomyoma-resembling stromal cell proliferation, leakage of prostatic secretion, infarction and prostatic calculi. Results: The mean preoperative (and postoperative) total PSA and free PSA levels were 6.1 ± 4.3 (1.14 ± 0.87) and 1.7 ± 1.6 (0.24 ± 0.19) ng/ml, respectively. The mean prostatic and transition zone volume was 83.9 ± 28.4 and 55.4 ± 27.6 cm3, respectively. Both total PSA and free PSA levels were correlated with total gland volume (p = 0.0001; p = 0.002) and the volume of the surgical specimen (p = 0.003; p < 0.05) and, upon stepwise logistic analysis, patients with a total gland volume of <50 cm3 had an odds ratio of 11 (CI 1.6–71.3) for having a free-to-total ratio of <18%. No minimal change pathology or prostatic inflammation were associated with preoperative total or free PSA levels. The free-to-total PSA ratio was higher in the group of patients with histologically acute and moderate to severe chronic-active prostatitis (mean ratio 27 ± 12%) than in patients with chronic-inactive prostatitis and minimal chronic-active prostatitis (mean ratio 0.19 ± 13%; p = 0.05), showing an odds ratio of 5 (CI 1.1–22.1) for having a free-to-total PSA ratio of <18%. Conclusions: Prostate volume and, in particular, transition zone volume seem to influence both free and total PSA levels in men with BPH. The free-to-total PSA ratio seems to be influenced by the presence of histological prostatitis in the surgical specimen. In particular, patients with a prostate volume of <50 cm3 and an inactive form of prostatitis seem to have a relatively higher risk of having a free-to-total PSA ratio of <18%.

Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: a critical overview

An overview of the placebo-comparative articles retrieved by a literature search on Medline - Embase - Biosis data banks from 1972 to 1993 was performed to evaluate the therapeutic relevance of the medical treatment with S-carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in patients with otitis media with effusion (OME). Ten original published studies were reviewed by an independent physician who assessed their quality by standard nine-items methodology. A meta-analytical approach was used to compare outcomes across all qualifying studies. Because of the heterogeneity of clinical endpoints, a new outcome measure was defined, i.e. overall clinical improvement, which consisted of the number of patients with complete resolution of clinical signs and symptoms and no need for surgical intervention. The objective evaluation criteria of normalisation of tympanogram was an additional end-point. Potential confounding variables such as eligibility criteria, treatment protocol and study design of the six methodologically complying studies were statistically homogeneous. No association was found between treatment effect-size and publication date or patients age. Outpatients with disease duration of < 6 months, not previously treated, with bilateral ear involvement were included in the studies; half of them presented hyperplasia or hypertrophy of the pharyngeal or the adenoid tissue. Out of 483 patients, 430 (89%) terminated studies and were evaluable. Results from this meta-analysis indicate that patients with OME receiving oral SCMC/-lys benefit from the medical treatment to the extent of avoiding surgical intervention approximately 2.31 times more often than similar patients receiving placebo (ratio of active drug to placebo-effect on overall clinical improvement: 2.31; C.I. 1.28-4.20, P < 0.01) and attain reversion to normal of the tympanogram at an extent close to statistical significance (odds ratio: 2.25, C.I. 0.97-5.22, P = 0.058). In conclusion, the use of this new methodology for the evaluation of the mucoactive drug effect in OME has shed light into methodological pitfalls of clinical trials to date and underlines the need for agreed outcome measures, which may modify medical policy, which addresses more and more often to symptomatic treatment.

EEG arousal pattern in habitual snorers with and without obstructive sleep apnoea (OSA)

This study evaluated the arousal pattern and sleep fragmentation in the sleep microstructure of heavy snorers and obstructive sleep apnoea (OSA) patients. Fifteen snorers [Group A, (A + H I) ≤ 10], 15 mild OSA (Group B, A + H I > 10 ≤ 30] and 15 moderate to severe OSA (Group C, A + H I > 30) were studied retrospectively analysing the number, duration and type of arousals according to scoring rules concerning definition (including delta bursts) and length (from 2 to 60 s) of phasic arousal events. The number of arousals per hour of sleep related to respiratory events was higher in Groups B and C, whilst in Group A there was a number of arousals not related to apnoea or hypopnoea. Daytime sleepiness, present in all three groups and measured by a subjective evaluation, correlated with both the number and EEG type of arousal, but not with the duration. Statistical analysis indicated that arousal index related to apnoea or hypopnoea was the best variable for determining the sleepiness risk in OSA and snorers. Sleep microstructure analysis seems a good scoring method for the detection of sleep fragmentation and arousals in relation to abnormal respiratory events.