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Biomedical subjects

M Cazzaniga

Publications and source records attributed to M Cazzaniga.

At least 55 records · Page 3Linked to original sources
PubMed1995

A randomized study of neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin compared to supportive care alone in patients with untreatable metastatic solid tumour.

Recent advances in our knowledge of psychoneuroimmune interactions involved in the control of tumour growth have shown the possibility of manipulating host anticancer defenses through a neuroimmunotherapeutic strategy. In particular, our previous studies have demonstrated that the concomitant administration of the pineal neurohormone melatonin may amplify the antitumour efficacy of interleukin-2 (IL-2) in humans. On this basis, a study was planned to investigate the influence of neuroimmunotherapy with low-dose IL-2 plus melatonin on survival time and on performance status in untreatable metastatic cancer patients. The study included 100 patients with metastatic solid tumours, for whom no standard therapy was available. They were randomized to receive IL-2 (3 x 10(6) IU/day subcutaneously for 4 weeks) plus melatonin (40 mg/day orally) or supportive care alone. Partial tumour regressions were seen in 9/52 (17%) patients treated with the immunotherapy, and in none of the patients treated with supportive care alone. The percentage of survival at 1 year was significantly higher in patients treated with IL-2 and melatonin than in those receiving the supportive care alone (21/52 versus 5/48, P < 0.005). Moreover, the performance status improved in 22/52 patients of the immunotherapy group and in only 8/48 patients treated with supportive care (P < 0.01). This study shows that cancer neuroimmunotherapy with low-dose IL-2 and the pineal hormone melatonin may prolong survival time and improve the quality of life of patients with metastatic solid tumours who do not respond to conventional therapies.

Administration, Oral↗
PubMed1995

Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone.

Recent observations have shown that the pineal hormone melatonin (MLT) may modulate oestrogen receptor (ER) expression and inhibit breast cancer cell growth. On this basis, we have evaluated the biological and clinical effects of a concomitant MLT therapy in women with metastatic breast cancer who had progressed in response to tamoxifen (TMX) alone. The study included 14 patients with metastasis who did not respond (n = 3) to therapy with TMX alone or progressed after initial stable disease (SD) (n = 11). MLT was given orally at 20 mg day-1 in the evening, every day starting 7 days before TMX, which was given orally at 20 mg day-1 at noon. A partial response was achieved in 4/14 (28.5%) patients (median duration 8 months). The treatment was well tolerated in all cases, and no MLT-induced enhancement of TMX toxicity was seen; on the contrary, most patients experienced a relief of anxiety. Mean serum levels of insulin-like growth factor 1 (IGF-1), which is a growth factor for breast cancer, significantly decreased on therapy, and this decline was significantly higher in responders than in patients with SD or progression. This pilot phase II study would suggest that the concomitant administration of the pineal hormone MLT may induce objective tumour regressions in metastatic breast cancer patients refractory to TMX alone.

Adult↗
PubMed1994

Vinorelbine as single agent in pretreated patients with advanced breast cancer.

Vinorelbine is a new semisynthetic vinca alkaloid with high activity against breast cancer. In this multicenter clinical study we evaluated the activity and toxicity of vinorelbine as a single agent in 30 advanced breast cancer patients pretreated with anthracycline and/or mitoxantrone (24 with recurrent tumor, 6 with non operable cancers). Vinorelbine was given at a weekly dose of 20 mg/m2 for a minimum of 3 weeks. Treatment was continued until there was disease progression or evidence of serious toxicity. Predominant sites of metastasis were viscera (14 cases), soft tissue (11 cases) and bone (5 cases). A median number of 12 doses of vinorelbine (range 3-34) were administered to each patient. Objective responses were recorded in 11 of them and 15 had minimal responses or stable disease. Four patients showed progression of disease during vinorelbine chemotherapy. The median duration of response was 5 months (2-14). The median survival time was 7 months (2-20+): 9 months for responders and 5 months for those with stable or progressive disease. The most important and dose-limiting toxicity was represented by leukopenia. The compliance of patients was very good and the treatment was well accepted by them all including those with low performance status. In conclusion, this study provides further evidence that a weekly schedule with vinorelbine as a single agent is effective and well-tolerated also in pretreated advanced breast cancer patients.

Adult↗
PubMed1994

Ondansetron does not stimulate prolactin release in breast cancer patients.

AIMS AND BACKGROUND: Prolactin (PRL) may be a tumor growth factor, mainly for breast cancer. The antidopaminergic drugs commonly used in the treatment of chemotherapy-induced vomiting stimulate PRL release, and this finding could represent a potentially negative biologic event for cancer patients. This study was performed to analyze PRL response to the serotonin-type 3 receptor antagonist ondansetron, a new active drug in the treatment of vomiting due to chemotherapy, in cancer patients. METHODS: The study included 8 premenopausal breast cancer patients undergoing adjuvant chemotherapy. Ondansetron was given intravenously at a dose of 8 mg, and venous blood samples were drawn at 0, 20, 60 and 120 min. The result were compared to those seen in 10 breast cancer patients treated with metoclopramide (10 mg. i.v.). RESULTS: PRL mean levels significantly increased in response to metoclopramide. In contrast, no significant changes in PRL mean values occurred after ondansetron injection. CONCLUSIONS: The study showed that ondansetron, whose efficacy in the treatment of chemotherapy-induced vomiting is well known, does not stimulate the tumor growth factor PRL in cancer patients, in contrast the the action of the most commonly used antidopaminergic drugs.

Adult↗
PubMed1994

[The ghost intraventricular obstruction. Its detection in the right ventricle by Doppler color].

INTRODUCTION: The Color Doppler echocardiography is a method of choice to detect the regional acceleration of flow in the left ventricle. The color study confirm it also in the right ventricle of infants with diseases other than hypertrophic cardiomyopathy. MATERIAL: We centered our attention in this finding observed in 16 infants with a mean age of 2.5 months (3 of whom were neonates) with several congenital heart malformations: 9 immediately after surgical ventricular septal defect closure (A-V canal type in 6, and isolated in 3); 2 with pulmonary atresia+intact septum+reconstruction of right ventricular-pulmonary artery connection; 2 with severe aortic stenosis; 1 with a double outlet right ventricle+pulmonary band; 1 with Jatene operation; finally 1 after balloon pulmonary valvuloplasty. RESULTS: The phenomenon consisted in a late Doppler systolic signal in the right ventricular apex whose velocity ranged between 1.5 and 2.9 m/s. The jet was directed towards the tricuspid orifice, with a normal pulmonary flow. The turbulence was easily viewed in the apical four chambers and subcostal sagittal plane of the right ventricle, the spectral signal showed a morphology with left side concavity. An erroneous diagnosis of apical ventricular septal defect was suggested in 2 cases in whom the left ventricular angiogram performed before treatment excluded the lesion. CONCLUSION: The dynamic nature of the jet suggest that an asynchronous order of myocardial contraction in hypertrophic right ventricule play a role in its genesis. With the increasing use of Doppler color technique, this finding can be observed with greater frequency in neonates and infants with operated or unoperated heart diseases and right ventricular hypertrophy. Apical ventricular septal defect will be included in the differential diagnosis.

Cardiac Catheterization↗
PubMed1993

Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract.

The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma.

Adult↗
PubMed1993

[Value of two-dimensional Doppler color echocardiography in mitral-ventricular-aortic obstructive disease in the newborn].

Over the last years, the bidimensional echocardiography has assumed an increasingly impact in the management of heart disease in neonates. With the addition of Doppler technique and color flow mapping this non invasive method provide the most accurate definition of cardiac anatomy and physiology. It is particularly true in newborns with left inflow or outflow obstruction disease such as: pulmonary vein stenosis, divided left atrium, mitral and aortic stenosis or atresia, subvalvular narrowing, and hypoplastic left ventricle and aortic tract. The combination of these two methods contribute to recognize a specific left cardiac abnormalities and allow us to evaluate the therapeutical success in the follow up period.

Aortic Valve↗
PubMed1993

[Percutaneous balloon valvotomy in neonatal obstructive cardiopathy. I: critical pulmonary valvular stenosis].

Percutaneous pulmonary balloon valvotomy using one balloon or more in sequential approach was attempted in 9 no selected neonates with critical pulmonary valve stenosis between March 1985 and October 1990 (mean age 10 + 8.6 days). The procedure was successful in seven of them (78%) in whom with a 1.22 + 0.2 balloon/annulus ratio the right ventricular systolic pressure decreased from 96 to 45 mmHg (p < 0.001), the transvalvular gradient from 65 to 23 mmHg (p < 0.001); and the systemic oxygen saturation increased from 69 to 86% (p < 0.001). In one patient the valve was not crossed. Two patients underwent surgery because unsuccessful balloon valvotomy result in the immediate and mid term period: hypoplastic right ventricle in one, and inferior vena cava thrombosis that prevent a second dilation in the other respectively. The mid term follow up showed a 62% (5/8) of successful result. Although the complex methodology and complications are not uncommon, the balloon pulmonary valvotomy is a safely and effective therapy for neonates with critical pulmonary stenosis.

Angiography↗
PubMed1993

[Percutaneous balloon valvotomy in neonatal obstructive cardiopathy. II. Critical aortic valve stenosis].

Percutaneous balloon aortic valvotomy using one or more balloons in sequential approach was attempted in 11 non selected neonates with critical aortic valve stenosis. The procedure was complete in 9 (81%), and they represent the study group with a mean age of 19 days. Using a balloon/annulus ratio of 0.86, the transvalvar gradient decreased from 49 to 25 mmHg, and left ventricular systolic pressure fell from 112 mmHg to 96 mmHg (p < 0.01, respectively). Fifty-five percent (5/9) of the patients developed a new aortic regurgitation, only one with grade 3. The maximal instantaneous Doppler gradient recorded in 7 neonates before and after valvotomy dropped from 67 to 35 mmHg (p < 0.01); while the left ventricular shortening fraction increased from 15 to 31% (p < 0.01). The Doppler gradient was correlated with the left ventricular shortening fraction (r:0.72) and the aortic regurgitation with the balloon/annulus ratio (r:0.82). The balloon pulmonary valvotomy was unsuccessful in 2 neonates (22%), both with hypoplastic left ventricle, both of which died in the operating room. Echocardiographic features of reestenosis were not found in the follow-up period (14 +/- 10 months); only one patient may need a future surgical intervention because significant aortic insufficiency. The pulmonary balloon valvotomy is a safe and effective therapy that must be used as the first step in the management of neonates with critical aortic stenosis in absence of hypoplastic left ventricle.

Aortic Valve Stenosis↗
PubMed1992

Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.

On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.

Adult↗
PubMed1992

Balloon pulmonary valvuloplasty in infants: a quantitative analysis of pulmonary valve-anulus-trunk structure.

OBJECTIVES: The present study was designed to establish possible predictors of unfavorable outcome in infants with pulmonary valve stenosis. BACKGROUND: Balloon pulmonary valvuloplasty is the treatment of choice for typical pulmonary valve stenosis. Patients with dysplastic valves may be less suitable candidates for this procedure because they have morphologic abnormalities of the complex valve-anulus-trunk that cause the obstructive phenomenon. METHODS: Twenty-five children (mean age +/- SD 1.1 +/- 0.7 years) with normal anulus diameter underwent balloon pulmonary valvuloplasty using a balloon/anulus ratio of 1.2 +/- 0.11. From the lateral view of a right ventricular angiogram, the following variables were quantified and scored: A, supravalvular narrowing; B, texture of the valve surface; C, diastolic deformity of the Valsalva sinuses; D, trunk/anulus ratio; E, systolic valve motion; and F, presence of a contrast jet. Paired t test, stepwise multivariate correlation with "dummy" variable methods were applied for both hemodynamic and valve-anulus-trunk determinations. RESULTS: The right ventricular-pulmonary artery gradient decreased from 66 +/- 21 (range 40 to 120) to 24 +/- 11 (range 10 to 50) mm Hg (p less than 0.001), whereas the right ventricular systolic pressure decreased from 89 +/- 20 (range 60 to 130) to 48 +/- 15 (range 30 to 80) mm Hg (p less than 0.001). Only variables A, B and D had significant influence in a percent reduction in right ventricular pulmonary artery gradient (R2 0.94, SEE 5.7; p less than 0.001). A score greater than or equal to greater than 4 obtained by adding the values from these three variables was correlated with poor outcome. CONCLUSIONS: These data show that there is an adequate relation between scores and outcome. We conclude that children less than 2 years old with pulmonary valve stenosis and a score greater than or equal to 4 should not be candidates for balloon pulmonary valvuloplasty.

Cardiac Catheterization↗
PubMed1984

Correlation of gonadal function with histology of testicular biopsies at treatment discontinuation in childhood acute leukemia.

Testicular open-wedge biopsy was performed in 35 children in complete remission from acute lymphoblastic leukemia without clinical signs of leukemic testicular infiltration at the time of treatment discontinuation. Histological investigation showed thickening of the tunica propria of the seminiferous tubules in 13 of 35 patients. In 5 of 35 patients, the tubular fertility index was markedly reduced; in 5 of 6 pubertal patients, decreased spermatogenesis or aplasia of germinal epithelium was observed. Histologic damage was found mainly in the germinal cells both in patients treated with cytosine arabinoside and cyclophosphamide and in those treated with antiblastic drugs not considered damaging to the gonads. The extent of impairment was independent of age at start of treatment. On the other hand, endocrinological investigation carried out at the crucial moment of treatment suspension showed normal hypothalamic-hypophyseal-gonadal function as well as normal anthropometric data, bone age, and pubertal stage in the majority of patients. Testicular leukemia was found in only one patient (2.8%) whereas three children with negative testicular biopsies had testicular relapses within 7 months. Therefore, in view of the limits of light microscopy in diagnosing leukemic infiltration at treatment discontinuation, we propose the use of more sophisticated techniques, possibly within 6 months of suspension of therapy.

Adolescent↗