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Biomedical subjects

A Calciati

Publications and source records attributed to A Calciati.

At least 37 records · Page 2Linked to original sources

[The evaluation of the end-ejection pressure-length relation as an index of regional contractility].

Although end-systolic pressure-length relationship (ESPLR) is now widely used as a regional substitute for the end-systolic pressure-volume relationship, there are some reservations about its use as an index of systolic performance. This study aimed at assessing whether by using end-ejection (zero aortic flow) as a definition of end-systole, ESPLR can be used to characterize myocardial performance independent of load, and if the choice of the region where to implant the sonomicrometers is critical. Ten anaesthetized dogs (16 +/- 2 kg) were instrumented with a left ventricular (LV) pressure micromanometer and an aortic flow probe. Sonomicrometers were implanted in the apical (L1) and the mid-ventricular (L2) regions of the anterior LV wall, and in the basal region of the lateral wall (L3). End-systolic pressure-length relationships were obtained during acute preload reduction induced by the inflation of a vena caval balloon. This evaluation was repeated after increasing end-diastolic pressure to 14-18 mmHg (delta PL), after increasing systolic pressure by 15 (delta P-I) and 25 mmHg (delta P-II) with graded descending aorta occlusion, and during dobutamine infusions at 2.5 (Db 2.5) and 5 micrograms/kg/min (Db5). End-systolic pressure-length relationships (r > 0.97; pressure range: 70-100 mmHg) were characterized by their slopes (Ees), the extrapolated intercept at zero pressure (L0) and the values of segment length at a pressure of 75 (L75) and 100 mmHg (L100). In all the myocardial regions studied by sonomicrometry, the increments in preload and afterload did not significantly shift ESPLR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Time course of pressure and flow in ascending aorta during ejection.

To analyze aortic flow and pressure relationships, 10 closed-chest anaesthetised dogs were instrumented with electromagnetic aortic flow probes and micromanometers in the left ventricle and ascending aorta. Left ventricular ejection time was divided into: time to peak flow (T1) (both pressure and flow rising), peak flow to peak pressure time (T2) (pressure rising, flow decreasing), and peak pressure to dicrotic notch time (T3) (pressure and flow both decreasing). These time intervals were expressed as percent of total ejection time. Load-active interventions rose markedly T2 (from 4.2 +/- 5.5 to 19.4 +/- 3.5 after phenylephrine (p less than 0.02); from 4.2 +/- 6.5 to 21.2 +/- 5.3 after dextran (p less than 0.02)). Conversely, dobutamine reduced T2 from 4.4 +/- 5.9 to -2.5 +/- 6.5 (p less than 0.05). Thus, during load-active interventions aortic pressure increases for a longer T2 time although forward flow is decreasing, as a result of higher aortic elastic recoil during ejection. Conversely, beta 1-adrenergic stimulation significantly shortens T2. Dynamic pressure-flow relationship is thus continuously changing during ejection. T2 seems to be inversely related to the efficiency of left ventricular ejection dynamics.

Animals↗

Pilot study of teniposide in combination chemotherapy for small cell lung cancer.

Teniposide is one of the most active agents in small cell lung cancer (SCLC). Because of the experimental evidence of synergistic activity between teniposide and methotrexate and between vincristine and methotrexate, 34 SCLC patients were treated with a combination of teniposide, vincristine, methotrexate and cyclophosphamide. Chest radiotherapy was given to responding patients with limited disease and prophylactic cranial irradiation was given to complete responders only. Most patients had extensive disease and good performance status. The main side-effects were myelosuppression, mucositis and peripheral neuropathy, which were all common and often severe. A response rate of 78% with 22% complete responses was obtained in 32 evaluable patients. Median durations of responses and survival were 252 and 311 days, respectively. Patients with limited disease had a median survival of 556 days while extensive disease patients had a median survival of 240 days. 2 patients with limited disease have been in continuous complete remission for more than 2 years from start of treatment.

Adult↗

[The variability of the heart rate, arterial pressure and peripheral circulation as the indices of autonomic control in essential hypertension].

In recent years the influence of autonomic nervous system on cardiac rhythm and blood pressure has been increasingly studied by analysis of cardiovascular fluctuations, particularly in diabetic and normal persons under various physiologic conditions, while still few data exist on essential hypertension. To characterize the autonomic cardiovascular control in essential hypertension we studied 22 untreated hypertensives, diagnosed within 1 year (mean age 43 +/- 2 years, mean +/- SEM) and 16 age-matched normotensives. Recordings of RR interval, breathing activity, noninvasive blood pressure (Finapres) and skin arteriolar flow (infrared photoplethysmogram) were obtained while in supine position and after sympathetic activation induced by passive transition to upright posture (tilting table). Autoregressive power spectral analysis was then carried out, and low- (0.03-0.15 Hz, LF) and high-frequency fluctuations (0.15-0.35 Hz, HF) were measured. LF and HF have been considered as markers of sympathetic and parasympathetic activity on the heart, respectively, and as markers of sympathetic and mechanic chest activity on the circulation, respectively. In supine position both cardiac and vascular variability were similar in both hypertensive and normotensive groups. After tilting however the increase in the sympathetic component of cardiac variability was blunted in hypertensives with respect to normotensives (hypertensives LFnu from 43.6 +/- 4.7 nu to 59.4 +/- 5.1 nu, p less than 0.005; normotensives LFnu from 36.9 +/- 3.3 nu to 83.4 +/- 2.6 nu, p less than 0.001), the increase in LFnu being statistically (p less than 0.001) reduced in the hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

4'-EPI-doxorubicin in advanced lung cancer. A phase II trial.

Fifty evaluable patients with advanced lung cancer (28 small cell and 22 non-small cell carcinomas), mainly pretreated by chemotherapy, received 4'-epi-doxorubicin 90 mg/m2 every 3 weeks. Two partial responses were obtained in small cell lung cancer patients, which lasted 153 and 168 days. Leukopenia, emesis and alopecia were the most frequent side effects. Two patients who previously received anthracyclines died suddenly of cardiac failure, another patient had severe congestive heart failure, and four others had minor cardiac dysfunctions. 4'-epi-doxorubicin has a modest activity in advanced lung cancer, mainly pretreated by chemotherapy and is not devoid of significant cardiotoxicity in this patient population.

Adult↗

Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise?

STUDY OBJECTIVE: The aim was to assess the changes in sympatho-vagal balance which occur with exercise. DESIGN: The power spectrum of RR interval fluctuations (low frequency [LF] and high frequency components [HF]) was determined before, during, and after graded work load exercise on a cycle ergometer. The power spectrum of the respiratory signal, oxygen consumption, and respiratory volumes were also evaluated. In all subjects HF was considered to be an index of respiratory sinus arrhythmia. In normal subjects HF and LF were considered to be indices of relative vagal and sympathetic activity, respectively, whereas in heart transplant subjects HF was considered as a respiratory modulation of the intrinsic heart rate, and not dependent on autonomic tone. Heart rate variability was evaluated as RR interval variance. SUBJECTS: 15 normal subjects (six trained cyclists and nine healthy sedentary subjects) and six orthotopic heart transplant recipients took part in the study. MEASUREMENTS AND MAIN RESULTS: During the first part of exercise, heart rate increased, RR interval variance decreased, HF decreased, and the relative amount of LF increased both in sedentary and athletic subjects, suggesting a relative increase in sympathetic tone. However, when approaching peak exercise, while heart rate further increased and the variance slightly decreased, the relative proportion of LF decreased and HF proportionally increased. At peak exercise HF accounted for 99.9% of heart rate variability in athletic subjects and for 88.9% in sedentary subjects (p less than 0.001 v baseline and v LF in both groups). In heart transplant subjects both the variance and the HF increased from the beginning of exercise (p less than 0.05), and showed a direct correlation with ventilatory variables and an inverse correlation with heart rate (r = 0.794, p less than 0.001, multiple regression analysis). No measurable LF components could be obtained in these subjects. During recovery, while the heart rate decreased and the RR interval variance increased, there was a relative increase in LF and a relative decrease in HF in normal subjects (either sedentary or athletic). Similarly, in heart transplant subjects, there was a decrease in HF during recovery. Thus the increase in HF at peak exercise in normal subjects contrasts with all the other data which suggest a prevalence in sympathetic tone during the entire exercise and the early recovery period, but appears similar to the increase in HF observed in heart transplant subjects due to the effect of increased ventilation during exercise. CONCLUSIONS: These findings suggest that at peak exercise a non-autonomic mechanism, possibly intrinsic to the heart muscle, may determine heart rate fluctuations in synchrony with ventilation in the intact as well as in the denervated human heart.

Adolescent↗

Doxorubicin and etoposide in the treatment of advanced measurable breast cancer.

Nineteen evaluable patients with advanced breast cancer were treated with a combination of doxorubicin and etoposide. Patients had measurable disease, received only mild pretreatment and most had good general conditions at start of therapy. Strict criteria for dose adjustments according to nadir counts were applied. A 42% response rate was obtained. Toxicity was mild and treatment well-tolerated. Doxorubicin-etoposide is an active regimen for patients with breast cancer and warrants further testing in a larger patient population with less stringent criteria for evaluation and treatment monitoring.

Adult↗

The role of induction chemotherapy in inoperable ovarian cancer.

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR + PR was observed in 24/30 (80%) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1%) patients had a complete macroscopic resection; 9/24 (37.5%) patients had a partial resection (residual tumor less than 2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28%. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.

Adult↗

Phase II study of divided-dose vinblastine in advanced cancer patients.

A better therapeutic index has been obtained in breast cancer patients when vinblastine is given by a 5-day continuous infusion program than by i.v. bolus; the continuous infusion pharmacokinetics has been reproduced by an iv divided bolus at 0 and 48 h, which may be more easily applied to outpatients. We performed a broad phase II study in 97 advanced cancer patients in which vinblastine was administered by i.v. divided bolus at 0 and 48 h at the starting dose of 3.5-4 mg/m2, every 3 weeks. Our aim was to confirm the results achieved by continuous infusion and to investigate the toxicity pattern of this novel administration schedule. Neurotoxicity and myelosuppression were the main side effects: constipation and peripheral neurotoxicity respectively developed in 28% and 38% of patients and were severe in 5% and 1%. Leukopenia and thrombocytopenia respectively occurred in 70% and 40% of patients and were severe in 11% and 4%. Four partial responses, 38 no changes and 42 progression were obtained out of 84 evaluable patients. Responses were seen in tumors of breast, lung, and head and neck. Our results do not support the use of vinblastine in divided doses in advanced cancer patients.

Adult↗

Acute haemodynamic effects of ibopamine and dopamine on isovolumic relaxation.

The effects of intraduodenal ibopamine (a new orally active inotropic agent claimed to have haemodynamic effects similar to dopamine) on isovolumic relaxation were monitored for 90 min in eight closed-chest anaesthetized dogs. Dopamine and epinine (ibopamine active metabolite) were also infused at graded doses. After 15 min, ibopamine (12 mg/kg) shortened the time constant of isovolumic relaxation, and increased stroke volume and mean aortic pressure. Peak positive dP/dt increased significantly only 10 min later. Heart rate did not change. Dopamine (10 micrograms/kg per min) similarly reduced the time constant, and increased stroke volume, mean aortic pressure, peak positive dP/dt and heart rate. Epinine (10 micrograms/kg per min) caused similar changes in peak positive dP/dt, stroke volume, mean aortic pressure, and accelerated time constant without raising the heart rate. Ibopamine and epinine therefore significantly improved the isovolumic relaxation phase, like dopamine, without however affecting the heart rate.

Animals↗

Isolated central nervous system metastasis from ovarian carcinoma: a case report.

Ovarian adenocarcinoma usually disseminates and recurs the abdominal cavity. The detection of central nervous system metastases is rare. In this report we describe a case of intracranial recurrence that developed during a complete local surgical and pathological response and was treated radically with surgery followed by radiation.

Adenocarcinoma↗

Lonidamine versus polychemotherapy in advanced non-small-cell lung cancer. A preliminary analysis.

No clear evidence of survival benefit has been definitely shown by chemotherapy in advanced non-small-cell lung cancer. We evaluated in a randomized trial the activity of the new drug lonidamine (up to 1050 mg/day) versus MVP (mitomycin C, 10 mg/m2, vinblastine, 5 mg/m2, cisplatin, 100 mg/m2). The preliminary findings on 25 patients showed that lonidamine can be easily administered at these dose ranges, and main toxicity was represented by myalgia and testicular pain. Tolerance to combination chemotherapy (MVP) was superimposable to our prior experience. Responses were recorded in both arms, and no survival difference was apparent. The study is in progress.

Adult↗

Phase II study of esorubicin in the treatment of patients with advanced sarcoma.

Esorubicin was administered to 12 patients with soft tissue sarcoma, 1 osteosarcoma and 1 desmoid tumor. Seven patients had never received chemotherapy before. Myelotoxicity was the main side effect, leukopenia being more pronounced than thrombocytopenia. No significant nonhematological toxicity occurred. Six patients had no change of median duration of 98 days and 7 patients progressed. The patient suffering from multiple-site lesions of a desmoid tumor obtained a long-lasting partial response. This study does not support further testing of esorubicin in sarcoma patients.

Antibiotics, Antineoplastic↗

Cisplatin and etoposide in chemotherapy-refractory advanced breast cancer.

Fourteen evaluable advanced breast cancer patients, extensively pretreated by chemotherapy, received a combination of cisplatin (DDP) and etoposide (VP 16). DDP was given at 60 or 100 mg/m2 on day 1, and VP 16 at 120 mg/m2 on days 1, 2 and 3; cycles were repeated every 4 weeks. Major responses were never obtained; a minor response in 1 patient, no change in 7 patients, and progression in 6 patients were observed. Main side effects were nausea and vomiting (62% severe), and leukopenia (31% leukocytes less than 2,000/mm3). Two patients refused further treatment due to intense nausea and vomiting. DDP-VP 16 combination chemotherapy is ineffective and poorly tolerated in heavily pretreated breast cancer patients.

Adult↗

Phase II study of divided-dose vinblastine in advanced breast cancer patients.

The pharmacokinetics of a 5-day, continuous infusion of vinblastine have been reproduced by an i.v. divided bolus at 0 and 48 h [10]; this schedule can be easily applied to outpatients. We treated 26 evaluable patients with refractory, advanced breast cancer with 3.5-4 mg/m2 vinblastine given i.v. by a divided bolus at 0 and 48 h of 21-day cycles. Neurotoxicity and myelosuppression were the main side effects: severe constipation and peripheral neurotoxicity developed in 14% and 3% of the patients, respectively; severe leukopenia and thrombocytopenia occurred in 24% and 10% of the patients, respectively. One partial response, 14 no changes, and 11 progressions were obtained. Our results do not support the use of vinblastine in divided doses in treating this disease.

Adult↗