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Biomedical subjects

M Santangelo

Publications and source records attributed to M Santangelo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Phase I dose escalation study of gemcitabine and paclitaxel plus colony-stimulating factors in previously treated patients with advanced breast and ovarian cancer.

Gemcitabine and paclitaxel (PTX) are among the most active new drugs in advanced breast and ovarian cancer. In this Phase I study, we used fixed doses of gemcitabine administered on days 1 and 8 and escalating doses of paclitaxel on day 1 of a 21-day cycle in patients with pretreated metastatic breast or ovarian cancer. The dose of gemcitabine was fixed at 1,000 mg/m2; PTX was commenced in the first small patient group at a dose of 90 mg/m2, which was then escalated in subsequent groups by 30 mg/m2 per step. From the third dose level onwards, all patients received granulocyte colony-stimulating factor 300 microg by subcutaneous injection on days 5 and 6, and granulocyte macrophage colony-stimulating factor on days 15-18. Cohorts of at least 3 patients were treated at each dose level. Dose escalation was stopped if at least a third of the patients in a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, or grade 3-4 non-haematological toxicity. The maximum tolerated dose (MTD) was defined as the dose level immediately below that causing DLT in one-third of the patients or more. Evaluation of the tumour response was performed every three cycles. Forty-five patients (31 with breast cancer, 14 with ovarian cancer) were treated at seven different dose levels. Only at the seventh PTX dose level was DLT observed after the first course of therapy: three grade 4 neutropenia, one grade 4 thrombocytopenia, and one grade 4 anaemia. DLT occurred in 5/6 patients at at PTX dose of 270 mg/m2; therefore dose escalation was stopped at that level and the dose immediately before it (PTX 240 mg/m2) was considered as the MTD and recommended for further studies. No toxic deaths occurred. Grade 3-4 uncomplicated neutropenia was observed in four patients. Three had uncomplicated grade 3-4 thrombocytopenia. One patient had grade 3 and one grade 4 anaemia. Nonhaematological side effects were generally mild. Among 30 evaluable patients with metastatic breast cancer, four complete responses (CR) (13%) and 12 partial responses (PR) (40%) were observed, for an overall response rate of 53% (95% confidence interval (CI) 34-72). The median duration of response was 31 weeks. Among 13 evaluable patients with advanced ovarian cancer, one CR (8%) and five PRs (38%) were observed, for an overall response rate of 46% (95% CI 19-78). The median duration of response was 32 weeks. Our study shows that gemcitabine and PTX can be administered in combination in patients with breast and ovarian cancer without unexpected toxicities and with encouraging therapeutic results.

Adult↗
PubMed1999

[Role of ultrasonography in the control of patients receiving perioperative total parenteral nutrition].

BACKGROUND: On the basis of personal experience and literature, this study has been carried out in order to clarify the impact of ultrasonography on the diagnosis and prevention of hepatobiliary complications Total Parenteral Nutrition (TPN)-related. METHODS: Between April 1995-April 1997 in the Department of General Surgery-University of Catanzaro, 18 adult patients submitted to major thoracic or abdominal surgery, underwent to TPN for perioperative time (range: 9-55 days). In these patients ultrasonography was performed at pre-established days in pre- and postoperative time in order to diagnose precociously the possibility of hepatobiliary complications. RESULTS: Ultrasonography showed: 3 cases of hepatic steatosis, 5 cases of steatosis and gallbladder biliary sludge, 2 cases of gallbladder biliary sludge alone, 1 case of gallbladder biliary sludge with microlithiasis, 1 case of acute acalculous cholecystitis. The other 6 patients presented only little laboratory tests alterations, but normal ultrasonographic findings. CONCLUSIONS: Therefore it is underlined the importance of systematic ultrasonographic follow-up of patients on TPN as a non invasive method in the early diagnosis of hepatobiliary complications TPN-related. The good compliance of the patients to this instrumental investigation and the not excessive increase of their management's costs are also underlined.

Adult↗
PubMed1998

Phase I/II study of paclitaxel and vinorelbine in metastatic breast cancer.

Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cancer no longer amenable to conventional treatment were entered into a phase I/II study in which the vinorelbine dose was fixed at 30 mg/sqm and paclitaxel was started at 90 mg/sqm and then subsequently escalated by 30 mg/sqm per step. Cycles were repeated every 21 days. Hematopoietic growth factor support was provided from the 4th dose level onwards. Grade III neutropenia was observed only in 2 patients treated at the 5th dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in all three patients treated at the 6th dose level. Other toxicities were mild. Paclitaxel 210 mg/sqm and vinorelbine 30 mg/sqm was the selected combination for phase II. Overall response rate in 34 evaluable patients was 38% (95% confidence interval (C.I.), 22% to 54%). In particular, 3 complete responses (9%) and 10 partial responses (29%) were observed. The observed level of antitumor activity, with an overall response rate of 38% and a median duration of response of 12 months, is of interest, since the study was targeted only to anthracycline-pretreated patients, most of whom had adverse prognostic features. The evaluation of a combination of vinorelbine and paclitaxel as first-line therapy in metastatic breast cancer seems worthwhile and is currently undergoing.

Adult↗
PubMed1997

Interactions between darodipine or isradipine and the 5-HT1A receptor agonist 8-OHDPAT in rat brain.

Isradipine and darodipine are dihydropyridine calcium antagonists that affect the serotonergic pathways with a peculiar profile of effects because, at low dose (0.08 and 0.3 mg/kg, respectively) they facilitate, but at high dose (1.60 and 5.0 mg/kg, respectively) they inhibit the serotonergic neurotransmission. To investigate the mechanisms of these effects, the selective 5-HT1A receptor agonist 8-OHDPAT was injected S.C. to rats pretreated I.P. with isradipine (0.04-1.60 mg/kg) or darodipine (0.3-5.0 mg/kg). By stimulating presynaptic 5-HT1A autoreceptor, 8-OHDPAT induced signs of inhibition of the serotonergic neutransmission (i.e., decrease of the 5-HIIA/5-HT ratio), but it also produced behavioral effects by stimulating postsynaptic 5-HT1A receptors (i.e., forepaw treadings). A low dose of isradipine (0.08 mg/kg) or darodipine (0.3 mg/kg) antagonized the presynaptic, but enhanced the postsynaptic effects of 8-OHDPAT, suggesting relief of the autoreceptor-mediated inhibition of the 5-HT release. Thus, the amine released could stimulate postsynaptic receptors, adding its action to that of 8-OHDPAT. A high dose of isradipine (1.60 mg/kg) or darodipine (5.0 mg/kg) left unchanged, or also enhanced, the signs of inhibition of serotonergic neurotransmission displayed by 8-OHDPAT, reducing but not suppressing the increase in the behavioral response to the stimulation of postsynaptic 5-HT1A receptors. It was speculated that the effects of isradipine and darodipine on scrotonergic pathways of rat brain could be due to changes in the back-regulation of the neurotransmission, mediated by 5-HT1A autoreceptors. This mechanism of action could be extended to other dihydropyridine calcium antagonists, because blockade of L-type VSCC by these compounds appears to be involved in their effects on brain 5-HT turnover.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Actions of nimodipine on the serotonergic systems of rat brain.

1. The effects of the serotonin (5-HT) precursor, L-5-hydroxytryptophan (L-5-HTP), or the selective 5-HT1A receptor agonist, 8-OHDPAT, on behavior or brain 5-HT metabolism or both were evaluated in rats IP pretreated with nimodipine at doses ranging from 0.31 to 40 mg/kg. 2. Nimodipine, in a wide dose range (0.6-20.0 mg/kg) potentiated the head-twitch response to L-5-HTP. 3. The effects of nimodipine on the 5-HT metabolism of rats treated with L-5-HTP did not comply with the increase in the behavioral response to this 5-HT precursor. 4. Nimodipine antagonized the effects on 5-HT metabolism induced by 8-hydroxy-2-(di-N-propyl-amino)-tetralin through stimulation of 5-HT1A autoreceptors. 5. It was concluded that the effects of nimodipine on brain 5-HT metabolism appeared to be linked to activation of serotonergic neurotransmission likely due to inhibition of the back-regulation mechanism mediated by presynaptic 5-HT1A receptors.

5-Hydroxytryptophan↗
PubMed1997

Motor evoked responses to paired cortical magnetic stimulation in Parkinson's disease.

We evaluated cortical excitability in patients with Parkinson's disease (PD) using paired magnetic stimulation. This recent technique allows to study the cortical inhibition after motor evoked potential (MEP) and its modulation at different intensities of stimulation and interstimulus intervals (ISIs). At low stimulus intensity and at ISIs of 40-75 ms we observed, in PD patients, a greater test MEP inhibition, which might be due to a lower facilitatory effect of conditioning MEP on the motor cortex. At high stimulus intensity, in PD patients, a consistent inhibition of test MEP persisted and, at ISIs of 75-150 ms, it did not reach the amplitude of conditioning MEP as in normal subjects. Some clinical and neurophysiological features, like a silent period of shorter duration, demonstrated in PD patients a decrease of the inhibitory input to the motor cortex. On the contrary, the persistence of test-MEP inhibition at high stimulus intensity could also suggest a prevalence of inhibitory activity when an effective and phasic activation of the corticospinal system is required.

Aged↗
PubMed1996

[Temporal arteritis associated with hyperthyroidism and complicated by angina pectoris. A case report].

A case of temporal arteritis is described in a woman of 67, affected by non insulin dependent diabetes mellitus, associated with polymyalgia rheumatica and complicated by angina pectoris. Angina, which appeared a few days after diagnosis, was coupled with electrocardiographic alterations, which did not seem sensitive to nitrates but went back when steroid at full dose was added. The patient was also affected by Basedow disease, which was present during the whole course of the vasculitis. Furthermore islet-cell antibodies (ICA) were present. HLA typing showed the presence of the B8, DR3 haplotype. The patient died after 22 months from the diagnosis of digestive hemorrhage, probably favoured by extended cortisone therapy, while signs of arteritis were still evident.

Aged↗
PubMed1995

Phase II study of high-dose epirubicin, lonidamine, alpha 2b interferon in advanced breast cancer.

44 patients with advanced breast cancer were treated with high-dose epirubicin (130 mg/sqm), because of its steep dose-response curve. Lonidamine and alpha interferon were administered as well with the aim of increasing epirubicin uptake and overcoming drug resistance. Granulocyte-colony stimulating factor support was provided. 14 complete responses and 22 partial responses were observed in 40 evaluable patients for a 90% overall response rate. Median duration of response was 12 months for complete responders, 7 months for partial responders. In two cases the complete response has lasted for more than two years. Myelosuppression, infection, and cardiac toxicity were the main treatment-related toxic effects. These results are encouraging enough to justify a randomized comparison of our chemotherapy program with standard regimens used in advanced breast cancer.

Adult↗
PubMed1995

A phase II study of carboplatin and vinorelbine as second-line treatment for advanced breast cancer.

Forty-one patients with advanced breast cancer were given carboplatin and vinorelbine as second-line therapy. Overall objective response rate was 46% (95% confidence interval 26-56%). Myelotoxicity was the most frequently observed toxic effect; grade III-IV leucopenia occurred in 46% of the patients. Our regimen is active as second-line chemotherapy for advanced breast cancer and warrants further evaluation.

Adult↗
PubMed1994

Pattern of motor evoked response to repetitive transcranial magnetic stimulation.

The changes in motor pathway excitability, induced by pairs or trains of transcranial magnetic stimuli, were studied. The motor evoked potential (MEP) pattern depended on the interstimulus interval (ISI), the stimulus intensity and the type of coil employed. At low intensity, using either an 8-shaped or a circular coil, there was a test MEP inhibition at ISIs of 50-150 msec. During trains of stimuli, this inhibition showed a periodic trend with an interval of 250-300 msec. At high stimulus intensity we observed a progressive disappearance of test MEP inhibition which was incomplete with an 8-shaped coil and complete, reaching an MEP facilitation, with a circular coil. The inhibition observed at low intensity might be due to cortical inhibitory mechanisms. The effect found at high intensity and with the circular coil could depend on the activation of deeper and at higher threshold cortico-spinal structures. This hypothesis, however, does not explain the simultaneous delay of the test MEP latency which might depend on the activation of different cortico-spinal pathways.

Adult↗
PubMed1994

Rapid-rate transcranial magnetic stimulation and hemispheric language dominance: usefulness and safety in epilepsy.

We performed rapid-rate transcranial magnetic stimulation (r-TMS) in 14 epileptic patients, using a coil centered over nine different positions on each side of the scalp and while the subjects counted aloud. We obtained lateralized speech arrest, concordant with the site of manual preference, in only seven patients. There was transitory homonymous hemianopia (one patient), brief jerking of one arm (two patients), and affective (crying) reaction (three patients) after the end of a train of stimuli. In our experience, r-TMS is not as sensitive as previously reported for determination of hemispheric language dominance and may have undesirable side effects.

Adult↗
PubMed1994

A critical appraisal of pathogenesis and morbidity of surgical treatment of chronic anal fissure.

Preoperative and postoperative manometric findings and the results of lateral internal sphincterotomy were analyzed in 44 consecutive patients affected with chronic anal fissure. Preoperatively, resting anal pressure was increased in 32 patients. At one month postoperatively, 23 patients showed normal pressures, whereas 14 were still hypertonic and seven, hypotonic. Only three patients still had a weak sphincter six months postoperatively. The overall morbidity rate was 31.8 percent. Minor complications occurred in 11 patients. Major complications affected three patients. Overall, impaired continence was recorded in eight patients, although only two complained of persistent, albeit lesser, defects of continence not requiring the use of pads. Nonoperative treatment should be reserved for few selected patients with recent, acute fissures. As for chronic and fissures, compared with other operative or nonoperative modalities of treatment, lateral internal sphincterotomy is a highly successful procedure and its minimal morbidity is well accepted by the patient.

Adolescent↗
PubMed1993

[Non-epithelial tumors of the colon-rectum. Our experience].

Non-epithelial malignancies of the colon and rectum are exceedingly rare. These neoplasms are usually asymptomatic and present with aspecific symptoms. Over a period of nearly 30 years (1963-1991) 1187 colorectal malignancies were treated surgically in our department. Twenty-one patients (about 2%) had non epithelial colorectal tumor: 8 lymphomas, 2 lipomas, 2 leiomyomas, 1 leiomyosarcoma, 4 neuroendocrine tumors and 4 "Tumor-like" lesions. Preoperative diagnosis could be made only in 5 patients. A retrospective analysis of our experience showed the importance of considering these lesions, though rare, among colorectal disease. Whenever an aspecific clinical picture with uncertain aetiology is showed and the patient scheduled for surgery, intraoperative histology is mandatory so as to guide any surgical strategy.

Colorectal Neoplasms↗
PubMed1993

Impact of computed tomography vs. intrarectal ultrasound on the diagnosis, resectability, and prognosis of locally recurrent rectal cancer.

The use of modern techniques of imaging in the postoperative follow-up is reported to allow an earlier diagnosis of local recurrence in patients operated on with anterior resection for rectal cancer and, consequently, to allow a higher percentage of local recurrence resection to be performed. Although intrarectal ultrasound (IU) has proved highly reliable in preoperative staging, its value in relapse detection has been investigated only in retrospective studies and rarely compared with that of computed tomography (CT). The present prospective study aims at evaluating the role of IU vs. CT in the diagnosis of local recurrence and at verifying whether an earlier diagnosis and a higher resectability rate of recurrence result in an acceptable long-term survival. Thirty-seven patients who had undergone low and ultralow anterior resection for rectal cancer (anastomosis within 10 cm of the anal verge) were investigated prospectively. All the patients have been followed up by IU and CT at predetermined intervals. Six local recurrences were detected. CT correctly identified all the local recurrences (sensitivity = 100 percent, specificity = 93 percent, and accuracy = 94.5 percent); IU correctly identified only four of six local recurrences (sensitivity = 66.6 percent, specificity = 93 percent, and accuracy = 89 percent). Four patients with local recurrence underwent surgical treatment (resectability rate = 66.6 percent). Abdominoperineal resection in three patients and Hartmann's procedure in one patient were performed. In the other two patients, extensive metastatic liver involvements contraindicated surgery. All the resected patients were alive after one year; two of them are disease free, and the other two experienced recurrent disease. In conclusion, CT seems to have a higher sensitivity and accuracy in relapse detection. The increase in the local recurrence resectability rate does not result in a significant improvement in long-term survival. However, the good quality of life justifies the high cost of an intensive follow-up and a more aggressive surgical approach.

Female↗