QT dispersion and early arrhythmic risk during acute myocardial infarction.

BACKGROUND: QT dispersion (maximal minus minimal QT interval calculated on a standard 12-lead electrocardiogram) has been suggested to reflect regional variations of ventricular repolarization and to provide a substrate for reentry ventricular arrhythmias. In this study we evaluate QT dispersion in patients with acute myocardial infarction and assess its relation with early severe ventricular arrhythmias. METHODS AND RESULTS: We studied 101 patients with acute myocardial infarction and a control group of 97 healthy subjects. We determined QT and QTc dispersion on the electrocardiograms performed 12 hours and 3 and 10 days after the onset of symptoms in myocardial infarction patients and on the control group. The average values of QT and QTc dispersion (measured hereafter in milliseconds, ms) were as follows: 70.5 +/- 42.5-87 +/- 46.6 (after 12 hours), 66.5 +/- 37.8-76.9 +/- 43.5 (on day 3), 68.9 +/- 42-76.3 +/- 43.8 (on day 10) and 44 +/- 13.4-54.2 +/- 16.3 (in control group). We observed statistically significant differences in QT and QTc dispersion between the electrocardiogram of normal subjects and each of the three electrocardiograms performed on patients with infarction (p < 0.0005, p < 0.005). We recorded a greater QT dispersion in patients with anterior infarction with respect to those with inferior/lateral infarction (79 +/- 38.6 vs 65.2 +/- 43.16, p < 0.05) and in patients with ejection fraction < 45% (93.1 +/- 28.4 vs 68.3 +/- 34.1 p < 0.005). During the first three days, QT dispersion did not differ in patients treated with thrombolytic agents with respect to those who were untreated, while on day 10 untreated patients showed higher values (74.9 +/- 45.3 vs 60.5 +/- 37.7, p < 0.05). Creatine kinase peak level, sex and age of the patients did not influence QT dispersion. Thirteen patients (12.8%) developed severe ventricular arrhythmias within 72 hours after infarction: 8 patients (7.9%) had ventricular fibrillation and 5 patients (4.9%) had sustained ventricular tachycardia. We found higher early QT and QTc dispersion values in patients who developed severe ventricular arrhythmias (108.8 +/- 63.2 and 125.8 +/- 68.5) with respect to patients who did not (63.3 +/- 32.9 and 80.8 +/- 38.9, p < 0.0005, p < 0.0005). CONCLUSIONS: Our data suggest that QT dispersion: 1) increases during acute myocardial infarction; 2) peaks in the early hours after symptom onset; 3) drops late after infarction in patients treated with thrombolytic agents; 4) is associated with early severe ventricular arrhythmias.

Current views on intravesical treatment and chemoprophylaxis of superficial bladder cancer. The present role of epirubicin and doxorubicin.

Since 1972, a large number of studies have shown that intravesical treatment with doxorubicin (adriamycin) is effective against carcinoma in situ and multiple papillary tumors. Furthermore, it significantly reduces the recurrence rate after transurethral resection. Its efficacy has been compared with that of Bacillus Calmette-Guerin (BCG), which is the only treatment accepted by the US Food and Drug Administration for therapy of carcinoma in situ (Tis). In more recent years, a few studies have been performed using intravesical epirubicin in the hope that different properties of the molecule might enhance the activity of the anthracyclines, but produce fewer and milder side-effects. After weekly instillations of epirubicin (50 mg in 50 ml of sterile water) a complete response is achieved in 47% of patients with a histologically proven papillary marker lesion. The prophylactic efficacy of even a single instillation of epirubicin within 6 hours after transurethral resection (TUR) was proved in a randomized study (30863) of the EORTC (European Organization for Research on Therapy of Cancer) Urological Group. A randomized Italian trial (Blinst 4) of chemoprophylaxis after TUR investigated the efficacy of different intravesical administration schedules of epirubicin (50 mg in 50 ml of sterile water). All treatment regimens were more effective than no treatment. The sequential intravesical combination of epirubicin and interferon-alpha-2b has shown, in our personal experience, encouraging clinical results and our laboratory data suggest the synergic activation of the local immune response.

[Concentration of aztreonam in plasma, urine, and seminal fluid of patients with chronic prostatitis]. / Concentrazioni di aztreonam nel plasma, nell'urina e nel liquido seminale di soggetti affetti da prostatite cronica.

The authors consider the concentration of antibacterial drugs in the seminal fluid as a reliable experimental model for the study of pharmacokinetics in chronic prostatitis (c.p.). The study was conducted on 32 subjects, 20 of whom were affected by c.p. and 12 were normal controls. All subjects were treated with aztreonam at a dosage of 1 g.i.m. The assay was performed 1 hour after the injection, on seminal fluid, urine and serum samples. No difference was observed between normal subjects and patients with c.p. with regard to serum and urinary levels of the drug. There was a trend towards a higher concentration of the drug in the seminal fluid of patients with c.p. when compared to normal subjects, with mean values of 1.8 and 0.9 mcg/ml respectively. This difference was not statistically significant. Furthermore, the drug concentration of the drug in semen was below the sensitivity limits of the assay in 43% of normal subjects and in 10% of patients with c.p. In the latter group of patients the mean values of aztreonam concentration exceeded the minimal inhibitory concentrations for most aetiological agents causing c.p. In conclusion, it is suggested that aztreonam is likely to be effective in acute prostatitis, caused by Gram negative strains and may be indicated in selected cases for the treatment of c.p.

Intravesical bleomycin in bladder tumour prophylaxis.

The authors have evaluated the efficacy, tolerability and systemic absorption of bleomycin administered by intravesical route in the prophylaxis of recurrences of superficial vesical tumours after endoscopic resection (TUR). Thirty mg of bleomycin dissolved in 30 ml of saline solution were instilled in the bladder once a week for the first month and then once a month for 12 months. The instilled fluid was held in the bladder for 1 hour. The systemic absorption of the drug was evaluated by a microbiological assay of bleomycin in plasma and in the perfusion liquid recovered from the bladder. Fifteen patients were treated; most had a long history of multiple recurrent tumours despite previous intravesical treatments. Thirteen patients presented tumour recurrences during the treatment; 4 of them were given a second course of instillations following a second TUR and 3 of these presented further recurrences. The authors conclude that the drug, administered intravesically to high-risk patients with the modalities employed in the present study, was not effective in preventing recurrences. It was well tolerated locally and was free from systemic toxicity. The amount of bleomycin that was not recovered from the bladder after a contact time of one hour was relatively high but the drug did not reach measurable levels in the peripheral blood.

Randomized comparative trial with ceftizoxime and cefotaxime in urinary tract infections.

Ceftizoxime, a new, semisynthetic, beta-lactamase-resistant cephalosporin, is not metabolized in man and is excreted almost entirely as the original active compound in the urine. The efficacy and safety of ceftizoxime were assessed in 80 patients with acute and chronic urinary infections, with and without associated pathological conditions, in comparison with cefotaxime. Two dosage schedules, 1 g or 0.5 g every 12 h, i.v. or i.m. for 10 days, were adopted according to the severity of each case and to separate randomization tables for each schedule; causal agents were all sensitive to both drugs in vitro. The overall results were excellent. Safety was excellent in almost all cases. In this trial ceftizoxime proved at least as effective and well tolerated as the reference antibiotic.

Treatment of bladder cancer with intravesical instillation of adriamycin.

Intravesical treatment with adriamycin has been extensively employed in the last decade. In the treatment of carcinoma in situ complete responses have been reported in about 60% of cases. Its efficacy is probably lower in the therapy of multiple or diffuse low stage transitional cell carcinoma that is too extensive to be completely resected by conventional transurethral surgery. In such circumstances, including cancer in situ, adriamycin compares favorably with other local forms of treatment. The prophylactic use of intravesical instillation of Adriamycin has been studied more extensively. Preliminary results of controlled randomized trials implemented from the EORTC Urological Group show that adriamycin instillations significantly reduce recurrence rate after TUR. The treatment is well tolerated. Systemic absorption is virtually absent, and no severe drug-related side effects have ever been reported. Chemical cystitis is occasionally observed, especially if multiple instillations are started immediately after TUR, or in the presence of additional inflammatory conditions, such as previous irradiation or bacterial cystitis.

Cooperative studies of chemoprophylaxis after transurethral resection of bladder tumors.

Large cooperative trials are more likely than series studied by small groups to bring about significant progress in the field of intravesical adjuvant chemotherapy of superficial bladder tumor. Multicenter randomized trials involving large numbers of patients have been conducted in Europe by the EORTC Urological Group. The Group's main objectives were to compare the efficacy of thio-TEPA, VM-26, epodyl, Adriamycin, and cisplatin, against no treatment, and to study the prophylactic effect of oral pyridoxine and evaluate the main prognostic factors. The results obtained so far are reported. Preliminary information is also given about the Blinst study, a multicenter open investigation of local chemotherapy with doxorubicin (Adriamycin), with special reference to evaluation of the importance of different modalities of treatment with a single drug.

[Echocardiographic study in congestive cardiomyopathy]. / Studio ecocardiografico della cardiomiopatia congestizia.

Single-dimensional echocardiography was used in the study of 15 patients with congestive cardiomyopathy. The main signs for the diagnosis of this disease and its differentiation from atherosclerotic coronaropathy were determined. Mitral and aortic echograms were examined along with the ventricular parameters in order to assess their importance in the study of ventricular function.