Biomedical subjects
Publications and source records attributed to A Costa.
A 23-year-old girl affected by Papillon-Lefèvre syndrome developed, during Etretinate therapy (1 mg/kg/day), two liver abscesses caused by pyogenic bacteria and a subphrenic abscess. The immunological effects of retinoids may precipitate severe infections in patients with Papillon-Lefèvre syndrome, who probably have a basic, even though not always evident, defect of PMN chemotaxis.
A controlled, randomized, double-blind, clinical trial has been performed in healthy volunteers in order to study the pharmacokinetics and tolerability of droxicam in comparison with piroxicam, when both drugs were administered at a dose of 20 mg/day for 20 days. Since transformation into piroxicam takes place in the gastrointestinal tract, unchanged droxicam was not detected in plasma. Steady state of plasma piroxicam concentrations was reached in all volunteers during the course of the study. Absorption kinetics of droxicam were delayed with respect to those of piroxicam (t1/2 a = 7.55 h for droxicam and 1.78 h for piroxicam). The remaining pharmacokinetical parameters studied showed no statistically significant differences. The bioavailability of both drugs was equal. Tolerability of droxicam and piroxicam was as usual for the NSAIDs, and no clinical or analytical side effects which could hinder its administration to wider populations were detected. Statistically significant differences in the number and type of side effects detected in the two treatment groups were not encountered.
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The 3H-thymidine labeling index (LI) was determined on 178 lesions, four of which were primary, from 129 patients with malignant melanoma. The overall analysis showed a wide variability of LI values, from 0.01% to 31.7%, with an exponential distribution and a median value of 8.0%. Similar median LI values were observed for the various metastatic sites, and no difference was found between patients who only had surgery and those who also received systemic therapy. Cell kinetics and patient age and sex were not related in terms of extent and type of nodal involvement. Conversely, a trend toward higher proliferative activity was observed in amelanotic (8.3%) than in melanotic (5.9%) lesions (P = 0.08). The follow-up study on a series of 48 Stage II patients has shown a higher probability of 2-year survival for patients with slowly proliferating tumors than for those with rapidly proliferating tumors (86.9% versus 40.4%, P = 0.054). Along with this finding, the absence of a relationship between cell kinetics and both the main host and tumor characteristics indicated that cell kinetics was a prognostic variable and could be an important tool in the evaluation of patients with metastatic melanoma.
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The authors report on 83 cases of intrathoracic metastases (ITM) observed as isolated first recurrences in a ten-year experience of periodic chest x-ray (CXR) survey of primary breast cancer. In 44 of 83 cases ITM were detected on CXR in absence of subjective symptoms or clinical signs (A) whereas 39 ITM cases were detected as subjectively (S) symptomatic in the interval between two planned CXR controls. Diagnosis was anticipated by CXR survey as the disease-free interval was significantly shorter (30 vs. 43 months, p less than 0.04) for A respect to S cases. Nevertheless such a diagnostic anticipation had no prognostic impact as the ten year survival from primary treatment did not differ (0.12 vs. 0.16, p = 0.6) between A and S cases. Multivariate analysis confirmed that no impact on survival from primary treatment is expected whether ITM are detected in an earlier (asymptomatic, preclinical) or in a more advanced (subjectively symptomatic) phase. CXR survey after primary treatment of breast cancer seems thus a very questionable policy.
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Preoperative detection of metastases in regional lymph nodes should constitute a fundamental step towards a better management of breast cancer. The National Cancer Institute of Milan has traditionally been engaged in this particular problem, that is, the search for a new imaging technique for detecting lymph nodal metastases from breast cancer. In 1984 axillary lymphoscintigraphy was performed on 26 patients with operable breast cancer by periareolar injection of 100 mu Ci of 99mTc sulphur microcolloid. The regional lymph nodes were identified as spot areas and a comparison was made between the number of primary draining axillary lymph nodes and their pathological examination. In only 2 of the 26 patients have more than 3 spot areas been revealed by axillary scintiscan, but this finding did not correspond to metastatic invasion. The lymphoscintigraphy pattern of the other 24 patients did not suggest any pathological condition. From our experience the method does not appear to help either a precise diagnosis of breast disease or the definition of the extent of mammary cancer.
To obtain more precise data on pulmonary doses in preparation for total body irradiation, the lung density of patients was systematically analyzed in treatment positions using data obtained by computed tomography (CT). With the patient supine, the lung density was not significantly different for the right and left lungs. In contrast, considerable differences were noted between the two lungs in lateral decubitus positions owing to variations in ventilation and perfusion. The relative electron density of lung was also found to decrease with age, dropping to pe = 0.160 at 71 years.
SISGRAD, the interactive computer system of the Antoine-Lacassagne Cancer Center Radiotherapy Department, has been operational since January 1982. It completes the computerized dosimetry system installed several years earlier and is fully integrated with the institution's central network. SISGRAD is in charge of surveillance of the radiotherapy treatments given by the Center's three radiotherapy units (1400 patients per year); it is also used for administrative purposes in the Department and physically connects all of the Department's operating stations. SISGRAD consists of a series of microcomputers connected to a common mass memory; each microcomputer is used as an intelligent console. SISGRAD was developed to guarantee that the treatments comply with prescriptions, to supply extemporaneous dosimetric data, to improve administrative work, and to supply banks with data for statistical analysis and research. SISGRAD actively intervenes to guarantee treatment quality and helps to improve therapy-related security factors. The present text describes the results of clinical use over a 4-year period. The consequences of integration of the system within the Department are analyzed, with special emphasis being placed on SISGRAD's role in the prevention and detection of errors in treatment prescription and delivery.
Plasma and dietary levels of retinol and beta-carotene were evaluated in a consecutive series of 47 females with histologically proven primary lung cancer and 159 nonneoplastic hospital controls. The dietary questionnaire included 69 different items: special care was given to foods rich in vitamin A and seasonal foods (e.g., vegetables and fruits), whereas serum analysis was focused on retinol and beta-carotene. Age-adjusted mean values for cases and controls were, respectively, 458.3 vs. 551.3 mg for plasma retinol, 276.1 vs. 390.1 mg for plasma carotene; 598.1 vs 820.6 mg for daily retinol, and 628.0 vs. 882.5 mg for dietary carotene. The odds ratios for low vs. high tertile, adjusted for age, smoking, retinol or carotene, cholesterol, and triglycerides by multivariate analysis were, respectively, 1.13 for plasma retinol, 5.04 for plasma carotene, 3.27 for dietary retinol, and 2.93 for dietary carotene. For all the examined items, there was a trend of increased risk for the second and third tertile, and statistical significance was reached for plasma beta-carotene (p less than 0.05). The hypothesis that a higher risk of lung cancer is related to a low vitamin A consumption is supported by these data.
This study was designed to define some biological aspects of cell suspensions, obtained by mechanical or enzymatic disaggregations, and to verify whether single cell suspensions are representative of original solid tumours. The study was performed on a series of 25 human solid tumours including breast carcinoma, ovarian carcinoma and malignant melanoma. A higher cell viability and a loss of aneuploid subpopulations, or a lower fraction of aneuploid cells, were observed in enzymatically-released samples than in samples obtained by the mechanical procedure. Moreover, the proliferative activity, which was generally similar for the cell suspensions obtained by the two disaggregation procedures, was always markedly lower in the cell suspensions than in solid samples from the same tumour. In conclusion, the results from this study indicate that many changes, such as selective release of cell populations from the tumour matrix, damage and destruction of aneuploid and proliferating cells can be induced to various extents by different disaggregation procedures.
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A flow cytometric study of DNA and protein contents was performed on cell suspensions obtained from 73 adult patients with non-Hodgkin lymphoma. Bivariate analysis identified a second subpopulation, not revealed by DNA determination, in 25% of the tumors. Protein heterogeneity was more frequently observed in diffuse than in nodular histology according the Rappaport classification and in high-grade than in low-grade malignancy tumors by the Kiel classification and the Working Formulation, but it was not related to ploidy or cell proliferative rate. The presence of an additional subpopulation, detected by protein analysis, defined as monoclonal by DNA analysis, could adversely affect clinical outcome in terms of response to treatment and overall survival.
Cell kinetics in transitional cancer of the bladder was studied in 35 patients by using the in vitro 3H-thymidine labeling index. The proliferative activity was remarkably lower than that observed for other human histotypes. Analysis of the relation between cell kinetics and histologic grading showed a value for grade III tumors two-fold that of grade I and grade II tumors. Cytogenetic analysis was possible in 15 cases, and different chromosome numbers from 40 to 120 and the presence of various structural aberrations were observed. When cytogenetic features were analyzed in relation to cell kinetics, higher proliferative activities were always associated with a loss of chromosome 13 and, except for one case, with a loss of chromosome 22.
Twelve patients with disseminated breast cancer were injected with monoclonal antibody MBr1 at the National Cancer Institute of Milan, Italy, from January 1983 to March 1985. The first seven patients had advanced disease and the remaining five operable breast cancer. In the first seven patients the initial dosage of MBr1 was 0.5 mg and was doubled in the next patient up to 16 mg. The last five women received 10 mg of MBr1. No general side effects such as bronchospasm, hypotension, immediate or delayed allergic reactions were observed. Four patients who were injected with 10 mg or more experienced fever, shudder and vague abdominal and articular pain. The following tests were monitored: R.B.C., W.B.C., percentage of lymphocytes, blood glucose, urea nitrogen and creatinine, serum levels of Na+, K+, Cl-, total proteins levels, albumins and globulins, bilirubin, GOT, GPT, alkaline phosphatase, LDH, amylase, gamma GT and CPK. No major modifications were observed: a limited increase of the transaminases, LDH and gamma GT was evident at the last check. An early temporary alteration of CPK was observed in the four patients who had symptoms. Serum levels of MBr1 are detectable immediately after injection starting from 4 mg, and all sera were negative 48 hours later. It is concluded that the scanty toxicity allows to continue clinical investigations to verify the linkage between MBr1 and Ca-MBr1 "in vivo" after a single injection of no more than 16 mg of the MoAb. The increase of this dosage as well as multiple injections do not seem safe at present.