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Biomedical subjects

M Cazzaniga

Publications and source records attributed to M Cazzaniga.

At least 19 recordsLinked to original sources
PubMed1998

Reduction of renal cortical blood flow assessed by Doppler in cirrhotic patients with refractory ascites.

The usefulness in cirrhotic patients of hemodynamic measurements by Doppler ultrasonography (US) is still not defined. We investigated the relationships between Doppler measurements and the severity of ascites. Portal blood flow velocity and volume, and hepatic and renal arterial resistance indexes (RI) were measured in 57 cirrhotic patients (19 without ascites, 28 with responsive ascites, and 10 with refractory ascites) and 15 healthy controls. The renal arterial RI were obtained for the main renal artery, interlobar vessels, and cortical vessels. Cirrhotic patients had decreased portal blood flow and an increased congestion index (CI). Only the CI was correlated to the severity of ascites, showing that it is also a reliable measure of the severity of portal hypertension in patients with ascites. The hepatic and renal artery RI were increased in cirrhotic patients, and the two values were correlated (r = .68; P = .00001). The RI of renal interlobar and cortical vessels were higher in patients with refractory ascites than in patients without ascites (P < .02 and P < .009), and correlated with sodium excretion rate (r = -.45; P < .003), the renin-aldosterone system, and creatinine clearance (r = -.62; P < .0002). The RI decreased from the hilum of the kidney to the outer parenchyma in healthy subjects and patients with responsive ascites, but this difference disappeared in patients with refractory ascites. This indicates that the degree of renal vasoconstriction varies in different areas according to the severity of the ascites. Cortical vessels are involved mainly in patients with refractory ascites, suggesting that the intrarenal blood flow distribution in cirrhosis tends to preserve the cortical area and that severe cortical ischemia is a feature of refractory ascites.

Adult↗
PubMed1998

[Clinical and echocardiographic impact of neonatal aortic valvuloplasty].

OBJECTIVES: The selection of patients for balloon aortic valvuloplasty is a vital clinical challenge in neonatal aortic stenosis. The present study was designed to establish possible predicting factors for poor results after balloon therapy. PATIENTS AND METHODS: 2D echocardiographic, Doppler color and clinical variables (grade of cardiac failure, aortic "anulus", mitral anulus, left ventricular diameter, ascending aorta, instantaneous Doppler gradient, and grade of aortic regurgitation) were analyzed in 32 neonates submitted to balloon dilation at 22 +/- 18 days of life. The evaluations were conducted during three periods in respect to balloon therapy (A: before; B: immediately after, and C: mid-term follow-up). The outcome in both, B and C periods was defined as favorable (all survivors with Doppler gradient < or = 70 mmHg and no other intervention on the valve) and unfavorable (death, first stage of univentricularization, valvular replacement or survivors with Doppler gradient > 70 mmHg). Mean values between subgroups were compared by Wilcoxon test; unconditional logistic regression was used to analyze the impact of cardiac failure and anatomic variables (continuous, categorized or Z) on the outcome. RESULTS: The Doppler gradient decreased from 70 +/- 28 to 34 +/- 14 mmHg after the valvuloplasty, and no changes were detected in the follow-up period (36 +/- 8 mmHg). An immediate favorable result was obtained in 72% of the patients; its consisted of 50% in period C. Nine neonates had an immediate unfavorable outcome (6 deaths and 3 with Norwood operation). In the follow-up, three patients had valvular replacement, one patient Doppler gradient > 70 mmHg and one patient with left ventricular endomyocardial abnormalities died. The severe cardiac failure (odds ratio: 33; CL 2.4-443; p = 0.008) and all categorized anatomic variables (aortic "anulus" < or = 6 mm; mitral anulus < or = 9 mm; ascending aorta < or = 8 mm; left ventricular diameter < or = 13 mm) were related with the immediate poor outcome. At 7.6 years, survival and freedom with no valvular replacement nor reintervention probability rates were 83% and 67%, respectively. CONCLUSIONS: 2D echo Doppler provides essential information about the anatomic and functional lesions coexisting with severe or critical aortic stenosis in neonates. Patients with left heart hypoplasia and severe heart failure should not be candidates for balloon valvuloplasty. The degree of residual aortic regurgitation and endomyocardial abnormalities of the left ventricle play an important role in the mid-term follow-up.

Aortic Valve Stenosis↗
PubMed1998

[Contribution of color Doppler in the diagnosis of bilateral ductus arteriosus].

We report a neonate with distal bilateral ductus arteriosus origin of nonconfluent pulmonary arteries which was only diagnosed accurately by 2-D echo Doppler color flow mapping in the context of situs ambiguous, univentricular A-V connection and pulmonary atresia with normal systemic/pulmonary venous drainage. The color flow appearance of this singular vascular anatomy was enhanced after prostaglandin administration, which, allowed us to see an image resembling a "moustache morphology". At 36 months of age, and after a successful bilateral 4 mm modified Blalock Taussig shunt implantation by sequential approach, the patient is waiting for the next surgical step which will include a restoration of the confluence of the pulmonary arteries with bidirectional Glenn operation. Brief embryological and differential diagnosis comments are discussed.

Anastomosis, Surgical↗
PubMed1998

Cytochrome P450 1B1 mRNA measured in blood mononuclear cells by quantitative reverse transcription-PCR.

Cytochrome P450 (CYP) 1B1 activates polycyclic aromatic hydrocarbons and aryl aromatic hydrocarbons to carcinogens. We describe a competitive reverse transcription-PCR (RT-PCR) assay for the quantification of CYP1B1 mRNA in blood mononuclear cells (BMCs) by simultaneous RT and PCR amplification of cellular RNA with decreasing amounts of an internal standard. The concentration of CYP1B1 mRNA is derived from the ratio between the intensities of the bands corresponding to the amplified products. To reduce the variability of mRNA extraction efficiency, the measured amount of CYP1B1 has been calculated in relation to the beta-actin gene products. We measured CYP1B1 expression in the BMCs of 75 human subjects; no significant differences in the CYP1B1:beta-actin ratio were detected between women (range, 0.47-4.35; median, 2.0) and men (range, 0.72-3.85; median, 2.09). The analytical imprecision (CV) of duplicates was 14% (n = 25 pairs), and the intraindividual CV for two samples, 1 month apart, was 22% (n = 20). No significant differences were detected in smokers (n = 25; range, 0.77-3.55; median, 2.14) compared with nonsmokers (n = 50; range, 0.47-4.35; median, 2.0). The method has a wide range of linearity, good sensitivity and precision, and is suitable for studies of individual susceptibility as indicated by CYP1B1 expression in BMCs.

Actins↗
PubMed1997

Evaluation of factors influencing 5-fluorouracil-induced diarrhea in colorectal cancer patients. An Italian Group for the Study of Digestive Tract Cancer (GISCAD) study.

Diarrhea is one of the dose-limiting toxicities for administration of fluorouracil (5FU) in patients with colorectal cancer and can result in severe morbidity and mortality. No well-defined prognostic factors influencing 5FU-associated diarrhea have been identified, which means its occurrence is unforeseeable. The aim of this study was to check whether any characteristics related to patients or chemotherapy could allow the identification of subsets of patients at higher risk of developing diarrhea while receiving a regimen containing 5FU. A logistic regression analysis was performed with age, sex, site of primary tumor, presence of primary tumor, presence of colostomy, time since surgery, number of courses of chemotherapy, diarrhea in previous courses, season of treatment, and chemotherapeutic regimens used as model parameters to predict occurrence of diarrhea in 258 colorectal cancer patients receiving a 5FU-containing regimen. Presence of primary tumor (P = 0.004), previous episodes of chemotherapy-related diarrhea (P = 0.00005) and summer season (P = 0.014) were found to be significant risk factors for developing diarrhea. The other variables examined, such as age, sex, chemotherapeutic regimen, site of primary tumor, presence of colostomy, and time since surgery, were not significantly correlated to diarrhea. Chemotherapeutic regimen was the only parameter that allowed prediction of the severity of diarrhea: 5FU/6S-leucovorin/interferon caused more severe diarrhea, followed by 5FU/leucovorin weekly. Although the analysis of these clinical features does not seem to allow the definition of a well-defined subset of colorectal cancer patients at higher risk of 5FU-induced diarrhea, it can be recommended that patients with primary tumor, or who have experienced diarrhea in earlier courses of chemotherapy or are receiving treatment in summer should be carefully monitored, especially in the first cycles.

Adult↗
PubMed1997

Acute effects of pamidronate administration on serum levels of interleukin-6 in advanced solid tumour patients with bone metastases and their possible implications in the immunotherapy of cancer with interleukin-2.

Bisphosphonates are potent inhibitors of bone resorption and are commonly used in the treatment of bone metastases. In addition, they seem to influence cytokine secretion. Since the efficacy of IL-2 cancer immunotherapy, in part, depends on endogenous cytokine secretion, bisphosphonates could be effective in modulating IL-2 activity. High pretreatment levels of IL-6 seem to correlate with resistance to IL-2. On this basis, a pilot study was performed to evaluate the in vivo effects of the bisphosphonate, pamidronate, on blood levels of IL-6. The study included 7 patients with bone metastases due to solid tumours. Pamidronate was injected intravenously at 60 mg over 3 h. Venous blood samples were drawn before, at 1-h intervals during pamidronate infusion, then after 1 and 3 days. Mean serum levels of IL-6 significantly decreased during pamidronate infusion, then after 1 and 3 days, IL-6 mean levels still remained lower than control level, but differences were not significant. This preliminary study shows that pamidronate infusion induces a rapid but transient decline in IL-6 blood concentrations, and suggests a possible use of bisphosphonates to modulate the efficacy of IL-2 cancer immunotherapy.

Aged↗
PubMed1997

Elective surgery for colorectal cancer in the aged: a clinical-economical evaluation.

A series of 56 consecutive patients, referred for surgery to a specialized institute, had elective laparotomies with various surgical procedures aimed at curing locoregional colorectal cancer. Data defining patient and tumour-related preoperative, operative and postoperative variables, including costs, were collected. The study group was divided into two age groups (< 65 vs > or = 65 years), which were similar in terms of patient- and tumour-related variables. Differences were not statistically significant (Pounds 440; 95% exact CI; Pounds -50; 1800). There is no evidence to suggest that there are any total charge differences in treating the two age groups, as confirmed by the cost analysis.

Aged↗
PubMed1997

Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone.

OBJECTIVE: Experimental and preliminary clinical studies have suggested that the pineal hormone melatonin (MLT) may stimulate hormone receptor expression on both normal and cancer cells. Moreover, MLT has appeared to inhibit the growth of some cancer cell lines, including prostate cancer, either by exerting a direct cytostatic action, or by decreasing the endogenous production of some tumor growth factors, such as prolactin (PRL) and insulin-like growth factor-1 (IGF-1). On this basis, a study was carried out to evaluate the clinical efficacy of a neuroendocrine combination consisting of the LHRH analogue triptorelin plus MLT in metastatic prostate cancer progressing on triptorelin alone. MATERIAL AND METHODS: The study including 14 consecutive metastatic prostate cancer patients with poor clinical conditions (median age: 70.5 years; median PS: 50%), refractory or resistant to a previous therapy with the LHRH analogue triptorelin alone. Triptorelin was injected i.m. at 3.75 mg every 28 days, and MLT was given orally at 20 mg/day in the evening every day until progression, starting 7 days prior to triptorelin. RESULTS AND CONCLUSIONS: A decrease in PSA serum levels greater than 50% was obtained in 8/14 (57%) patients. Moreover, PSA mean concentrations significantly decreased on therapy of triptorelin plus MLT. In addition, a normalization of platelet number was obtained in 3/5 patients with persistent thrombocytopenia prior to study. Mean serum levels of both PRL and IGF-1 significantly decreased on therapy. Finally, a survival longer than 1 year was achieved in 9/14 (64%) patients. This preliminary study would suggest that the concomitant administration of the pineal hormone MLT may overcome the clinical resistance to LHRH analogues and improve the clinical conditions in metastatic prostatic cancer patients.

Administration, Oral↗
PubMed1997

[Clinical response and survival in metastatic renal carcinoma during subcutaneous administration of interleukin-2 alone. Subcutaneous Il-2 in renal carcinoma].

Several clinical studies have demonstrated the efficacy of subcutaneous immunotherapy with Il-2 alone in metastatic renal cell carcinoma (RCC). In an attempt to better define the clinical parameters which may predict the efficacy of treatment, the present study shows the results obtained with subcutaneous Il-2 alone in 91 evaluable metastatic RCC patients. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days/week for 6 weeks, corresponding to one immunotherapeutic cycle. In nonprogressing patients, a second cycle was given after 28-day rest period. A complete response (CR) was achieved in 2/91 patients. Moreover, 19/91 patients had a partial response (PR). Therefore, objective response (OR) rate was 21/91 (23%) patients. Stable disease (SD) was achieved in 41 patients, while the remaining 29 patients had a progressive disease (PD). OR rate was significantly higher in patients with a long disease-free survival than in patients with synchronous metastases, in nephrectomized patients than in the non-nephrectomized ones, and in patients with high than in those with low PS. The survival obtained in patients with CR or PA was significantly longer with respect to that found in patients with SD or PD. The toxicity was substantially low in all patients. This study confirms that the subcutaneous immunotherapy with IL-2 alone is an effective and well tolerated therapy of metastatic RCC.

Adult↗
PubMed1997

Prevalence and incidence of cholelithiasis in patients with liver cirrhosis.

AIMS: To evaluate the prevalence, the incidence and the history of cholelithiasis in liver cirrhosis. PATIENTS AND METHODS: A series of 233 consecutive cirrhotic patients (193 Child A, 35 Child B and 5 Child C) were assessed for cholelithiasis by ultrasonography. Of these, 201 (those who had never had cholecystectomy) were followed-up with repeated ultrasonographies. RESULTS: The prevalence of cholelithiasis was 38% (22% gallstones and 16% previous cholecystectomies). No relationships with the usual risk factors for cholesterol gallstones, such as age, sex, body mass index, serum glucose or triglycerides, were found. On the contrary, close correlations were observed with serum albumin, bilirubin, prothrombin time and Pugh score. By multivariate analysis, only serum bilirubin was independently correlated with cholelithiasis. Histories of biliary pain were more frequent in patients with previous cholecystectomy (62% cases) than in those with gallstones (21%) and those without cholelithiasis (7%). On the contrary, complaints of dyspepsia were similar in the three groups of patients. During a mean follow-up of 34.4 +/- 0.9 months, there was a 4.9% annual rate of development of new stones in 127 patients without cholelithiasis at the first investigation. This rate is markedly higher than that reported for normal subjects in a previous survey carried out in a similar geographic area. During a mean follow-up of 31.8 +/- 1.2 months, symptoms or complications were seen in 2 out of 45 patients with initial gallstones (4.4%). The annual rate of complications was estimated to be less than 2%. CONCLUSIONS: Cholelithiasis is frequently associated with cirrhosis and the risk of developing new stones remains high during the natural history of the disease.

Bilirubin↗
PubMed1996

Long-term administration of isosorbide-5-mononitrate does not impair renal function in cirrhotic patients.

Isosorbide-5-mononitrate (Is-5-Mn), alone or combined with beta-blockers, has been proposed for prophylaxis of variceal bleeding in cirrhosis. However, renal insufficiency, might be an important undesirable effect of this therapy, especially in patients with ascites. We assessed the changes in renal function induced in 26 cirrhotic patients by acute or chronic administration of Is-5-Mn. The acute administration of 20 mg of Is-5-Mn to 21 patients reduced mean blood pressure (83.4 +/- 2.4 vs. 92.8 +/- 3.4 mm Hg, P < .001), urine volume (5.5 +/- 0.8 vs. 8.7 +/- 1.1 mL/min, P < .05), urine sodium excretion (114 +/- 19 vs. 244 +/- 41 muEq/min, p < .001), urine potassium excretion (41 +/- 3.4 vs. 67 +/- 8.5 muEq/min, P < .001), and atrial natriuretic factor (74 +/- 10 vs. 98 +/- 12 pg/mL, P < .005). The glomerular filtration rate was decreased in the 11 patients with ascites (57 +/- 9 vs. 68 +/- 12 mL/min, P < .05), and plasma renin activity was increased in 4 ascitics. Twenty-one patients (16 from the acute study + 5 other patients) were given Is-5-Mn for 3 months at the dose of 80 mg/d. This did not affect blood pressure and renal function in patients without ascites, but reduced mean blood pressure (91.9 +/- 3.4 vs. 89.6 +/- 3 mm Hg, P < .05), urine volume (5.8 +/- 1.1 vs. 3.4 +/- 0.9 mL/min, P < .05), and urine sodium excretion (205 +/- 38 vs. 99 +/- 16 muEq/min, P < .01) in those with ascites. There were no changes in glomerular filtration rate and renal plasma flow, while plasma renin activity increased in only 3 patients with ascites and 1 without. Systemic hemodynamics and renal function of cirrhotic patients, especially those with ascites, are affected adversely by acute administration of Is-5-Mn. Long-term administration of the drug is well tolerated by compensated patients and does not affect renal plasma flow nor glomerular filtration rate, but can induce hypotension and sodium retention in patients with ascites.

Ascites↗
PubMed1996

Prevention of variceal rebleeding and treatment of liver carcinoma by consecutive transjugular intrahepatic portosystemic shunt and hepatic artery chemoembolization.

Variceal bleeding and hepatocellular carcinoma are two severe complications of cirrhosis. One of our patients who bled from oesophageal varices was found to have a malignant hepatic nodule. As the patient refused liver transplantation, a transjugular intrahepatic portosystemic stent was carried out for portal hypertension, and transcatheter arterial chemoembolization for cancer. Both procedures were successful and one year later liver function has not deteriorated. This case shows that intrahepatic stent placement and selective arterial chemoembolization can be safely performed in cirrhotic patients with a solitary hepatocarcinoma nodule and a good liver function reserve.

Aged↗
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↗