Biomedical subjects
Publications and source records attributed to A De Matteis.
According to cirrhotic patient's hyperkinetic circulatory state and to different pathophysiologic moments of kidney and liver failure, it is suggested that in cirrhosis a vasoactive balance is changed to more active vasodilatation. Also calcitonin gene-related peptide (CGRP) is likely involved in this change.
It is reported a review on side effects and toxicity of alfa interferon in treatment of chronic viral hepatitis. The clinical experience in 44 patients affected by chronic hepatitis and treated with 3MU of alfa interferon is analysed.
BACKGROUND: Oophorectomy is one of the treatments of choice for premenopausal women with advanced breast cancer. However, in recent years LH-RH analogs have replaced surgical castration (or ovarian irradiation) on the basis of the comparable therapeutic activity shown by these drugs in phase II studies. Moreover, the combination of tamoxifen and LH-RH analogs has gained popularity among clinicians attempting to obtain a 'total estrogen blockade' according to the same rationale previously proposed for advanced prostatic cancer. However, it has thus far not been proven that medical castration is as effective as oophorectomy or ovarian irradiation, nor is there enough evidence that tamoxifen could improve the efficacy of ovarian ablation. PATIENTS AND METHODS: Eighty-five perimenopausal patients with estrogen receptor or unknown positive metastatic breast cancer were randomly allocated to receive one of the following treatments: surgical castration (or ovarian irradiation); goserelin; surgical castration (or ovarian irradiation) plus tamoxifen; goserelin plus tamoxifen. The study was performed according to a 2 x 2 factorial randomised design. RESULTS: While overall there was no significant difference in the response rates observed after two by two grouping, a trend did favour oophorectomy (or ovarian ablation) with respect to treatment activity. In fact, the best response rate was observed in patients allocated to this treatment (46.6% OR -95% CL: 21.2-72.9) while the lowest rate was observed in patients treated with oophorectomy plus tamoxifen (11.1% OR: CL: -3.4-25.6). Response to goserelin and goserelin plus tamoxifen was 27.2% (+/- 18.6) and 45% (+/- 21.8), respectively. Logistical regression analysis suggested that there might be a different interaction between tamoxifen and goserelin or oophorectomy (ovarian irradiation), respectively. Nevertheless, patient survivals were comparable, irrespective of allocated treatment. This indicates that two by two grouping has some value with respect to treatment efficacy and shows that oophorectomy (or ovarian irradiation) and goserelin have comparable efficacies. Tamoxifen did not improve the efficacy of gonadal ablation, although it did enhance the activity of goserelin treatment. CONCLUSIONS: The results of the present study confirm prospectively that the efficacy of chemical castration is comparable to that of oophorectomy (or ovarian irradiation). The concurrent use of tamoxifen can probably enhance the activity of goserelin, but it also induces more side effects. However, it doesn't appear that 'total estrogen blockade' is more effective than gonadal ablation alone. Indeed, the question of whether chemical and surgical castration have the same effect in breast cancer is still open as is the one concerning the interaction between tamoxifen and gonadal ablation. Both questions should be addressed by prospective studies.
AIMS AND BACKGROUND: The aim of the present study was to determine, retrospectively, whether the immunohistochemical expression of two biologic markers of aggressively, P-glycoprotein (P-gp) and PCNA/cyclin (PCNA), could be related to response to chemotherapy and prognosis in locally advanced breast cancer. METHODS: PC 10 Mab was used to determine the proliferation index (PCNA) and C-219 Mab to determine P-gp in 25 locally advanced breast carcinomas subjected to preoperative chemotherapy with MDR-related drugs. RESULTS: P-gp and PCNA were expressed in 76% and 100% of the tumors, respectively. No case of high P-gp expression was associated with good chemosensitivity, and all P-gp-negative cases showed the best chemotherapeutic response. P-gp and PCNA were both highly expressed in patients who developed local-regional or distant metastases. No recurrence was associated with a negative or low P-gp score. CONCLUSIONS: Statistical analysis showed that high P-gp expression was related to a poor response to chemotherapy and a short disease-free survival. A high PCNA score was not found to be significant for predicting chemosensitivity or survival.
Three patients with recurrent hyperparathyroidism (15, 8 and 3 years respectively, after the first operation) are described in order to establish the causes and define the clinical characteristics of the disease. The observation that in the present series recurrent hyperparathyroidism was associated either with an adenoma (two cases) or a carcinoma (one case), appears to stress the possibility of the pathological involvement of one gland even though recurrent hyperparathyroidism should be considered due to the chronic extrinsic stimulation of the parathyroid glands. The severity of the clinical and metabolic picture observed at the time of the first diagnosis and/or at the time of recurrence together with the simultaneous presence of bone and stone disease in the patients described is of particular interest. The cases reported underline the importance of carrying out careful metabolic investigations in patients with hyperparathyroidism not only before but also for a prolonged period of time after operation.
Serial immunologic tests (active E-rosettes = T-Ea; total E-rosettes = T-Et; total lymphocytes and null cells) were performed every 3 months for 5 years on 113 melanoma patients. A significant reduction in absolute T-Ea, T-Et, null cells, and total lymphocytes was noted in the patients who died, by comparison with those who are still alive. The latter presented a significant reduction in absolute T-Et only, plus a significant increase in null cells when compared with normals. The 38 patients without metastases, at the end of the study, presented a reduction in T-Et and an increase in null cells compared with the normals, while the 75 patients with metastases presented a reduction in T-Et, null cells and total lymphocytes when compared with the patients without metastases and a reduction in T-Ea, T-Et, and total lymphocytes when compared with the normals. Null cells show a linear decrease in patients who died and a linear increase in those who survived. A total of 80.2% of patients with a fall in T-Et displayed metastases usually within 2 to 10 months (mean, 6.8). Patients with normal T-Ea, T-Et, and total lymphocyte values showed a significant prolonged survival when compared to those with lower values. In addition, survival seemed to be always a function of immunologic test values, irrespective of the tumor site.
The calcified keratin in the horn pearls of a glans carcinoma has been studied by histochemical and ultrastructural methods. The former have shown that the calcified areas contain glycoproteins and acid proteoglycans and have a concentration of sulphydryl groups greater than that of the surrounding, uncalcified keratin. Electron microscopy has shown the presence of intracellular needle- and filament-like crystals closely related to the keratinocyte filaments and similar to those found in other calcified tissues. Besides the close relationship discovered between crystals and keratinocyte filaments, the other main conclusions are that keratin calcification is an intracellular process and that keratin molecules are responsible for the induction and regulation of the process.
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In the elderly, systemic hypertension is the main risk factor for cardiovascular diseases. Left ventricular hypertrophy, the most common adaptation to chronic pressure overload, has been recognized as an independent risk factor for an increased incidence of sudden death and arrhythmic disturbances. This study compared the prevalence of serious ventricular arrhythmias in elderly individuals with uncomplicated hypertension and in normotensive age-matched controls, using left ventricular mass index (LVMI) to differentiate patterns of anatomic adaptation to systolic, diastolic, or systolic-diastolic hypertension. The study enrolled 378 consecutive untreated elderly subjects (> or = 65 years of age), without clinical evidence of heart failure; 203 were hypertensive and 175 were normotensive. Each participant underwent standard 12-lead electrocardiography, M-mode and B-mode echocardiography, and 24-hour ambulatory electrocardiographic monitoring. Serious, statistically significant arrhythmias (Lown classes > or = 3) were present in 6.8% of normal subjects versus 17.1% of individuals with systolic, 31.5% of those with diastolic, and 20.4% of participants with systolic-diastolic hypertension. Arrhythmias did not differ in terms of left ventricular morphologic patterns or LVMI or between subgroups of hypertensive patients. Our data support the hypothesis that the pathogenesis of arrhythmias is related not to the electrophysiologic derangement of hypertrophied muscle but, rather, to the effects of hypertension on the cardiac structure. Cardiac fibrosis, one of the deleterious events accompanying hypertension, may be the main substrate for ventricular arrhythmias.
Myotonic dystrophy (MD) is associated with a wide spectrum of cardiac abnormalities, but only a few longitudinal studies have investigated the natural course of heart disease in MD. To assess whether neuromuscular involvement significantly predicts cardiac disorders in MD, 83 patients with various grades of disease severity were enrolled in a 13-year follow-up study (mean, 60.6 +/- 37.8 months) that included periodic physical and instrumental cardiac examinations (standard and Holter electrocardiography, echocardiography). During follow-up, muscular disease worsened clinically in 9 patients (11%) whose baseline severity grade changed accordingly; only 3 of them demonstrated parallel worsening of cardiac disturbance, however, compared with a large number of patients who showed additional cardiac abnormalities. These included further worsening of pre-existing pathologic features (19/83) and the appearance de novo of serious arrhythmias and/or conduction defects (23/83). Pacemaker implantation was necessary in 11 of 83 patients (13.2%) who had symptomatic bradyarrhythmias, bifascicular block, and P-R prolongation with a His-to-ventricle interval exceeding 55 ms, as documented by electrophysiologic study. Eight (9.6%) patients died: 2 from noncardiac and 1 from unknown causes, 1 from heart failure, and 4 from sudden death closely related to documented ventricular tachycardia. The incidence and seriousness of arrhythmic and conduction disturbances correlated with the severity of the muscular involvement. Nevertheless, cardiac and muscular disease did not show a linear progression. Cardiac involvement generally worsened more rapidly than did skeletal muscle disease.
Data currently available are insufficient to demonstrate a real utility for CA 15-3 in the diagnosis, staging or surveillance of breast cancer patients following primary treatment. The aim of this study was to determine if there was a correlation between supranormal CA 15-3 serum levels and clinical and biological variables in breast cancer patients at first disease relapse. From October 1988 to March 1998, 430 consecutive patients entered the study. Overall CA 15-3 sensitivity was 60.7%. Elevated CA 15-3 levels were found more frequently in patients with liver metastases (74.6%) and in those with pleural effusion (75.7%). CA 15-3 sensitivity was 70.4% in patients with estrogen-receptor-positive (ER+) primary tumors and 45.9% in those with estrogen-receptor-negative (ER-) tumors (p < 0.0001). In patients with a limited extent of disease, marker sensitivity was 57.7% in ER+ tumors and 25.7% in ER- tumors (p < 0.0001). Logistic regression analysis showed ER status, disease extent and pleural effusion as independent variables associated with CA 15-3 positivity. The multivariate Cox analysis showed ER and disease extent as independent variables predicting overall survival, whereas CA 15-3 failed to be statistically significant. CA 15-3 was an independent variable only when the disease extent variable was removed. This study suggests that CA 15-3 in advanced breast cancer patients is a marker of both disease extent and ER status. The direct relationship with ER status indicates that CA 15-3 diagnostic sensitivity in the early detection of disease recurrence could be greater in ER+ patients than in ER- ones. Furthermore, this suggests that patients with elevated CA 15-3 levels could have disease that is more sensitive to hormone manipulation than those with normal CA 15-3 values.
The effect of bradykinin (BK) on myocardial inotropic state was tested on 5 isolated rat heart preparations, in which a proper ballon was placed to record left ventricular pressure, whose developed systolic value was taken as an index of contractility. A reduction of developed left ventricular pressure was observed when BK was added to the perfusion oxygenated Tyrode solution. However, when BK was given after 1-amino-benzotriazole, an inhibitor of Cytochrome P-450 (Cyt P-450), developed pressure did not change. Since Cyt P-450 is known to act on arachidonic acid inducing the production of epoxiecocistrienoic acids (EETs) which hyperpolarizes myocardial fibres, it was argued that the reduction in contractility by bradykinin was the result of the hyperpolarizing effect of EETs. The fact that the concentration of Cyt P-450 is higher in the vascular endothelial cells than in the sarcolemma of the myocytes and the observation that the coronary resistance decreases together with the contractility suggest that the endothelium plays a pivotal role in mediating the negative inotropic effect of BK.
BACKGROUND: Prognosis of advanced ovarian cancer is unsatisfactory. Chemotherapy can be intensified combining active drugs at their highest possible doses. PATIENTS AND METHODS: In this phase I/II trial, 77 untreated patients received escalating doses of paclitaxel (135, 155, 175, 195 and 215 mg/m2, infused over 3 hours) with carboplatin (AUC 3.6) and cisplatin (60 mg/m2). Nine, 16, 13, 8 and 3 patients were treated at the five levels, respectively. A further 28 patients were treated at the maximum tolerable dose (MTD). RESULTS: Dose-limiting toxicities (one WHO grade 3 constipation, one grade 2 prolonged peripheral neurotoxicity and one grade 3 cardiac toxicity) occurred at 215 mg/m2 in 3 out of 3 patients. MTD was reached at level 4 paclitaxel dose (195 mg/m2). Response was evaluated in 62 patients. A complete response was achieved in 23 patients (37.1%-95% CI 25.2-50.3), including 16 (25.8%) pathological and partial response in 28 (45.2%), for an overall response rate of 82.3% (95% exact CL: 70.5%-90.8%). The probability of response was affected by the degree of initial debulking (p = 0.002) and not by the paclitaxel dose. In patients with stage III-IV disease, median progression-free survival was 17 months (95% CI 14-25). After a median follow-up of 28 months, median survival had not been reached; 2-year estimated survival was 67%. CONCLUSION: Paclitaxel can be safely given at the dose of 195 mg/m2 in combination with carboplatin (AUC 3.6) and cisplatin (60 mg/m2). This combination is active and safe and could be considered in clinical settings requiring intensive short treatment.