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Biomedical subjects

M Pagano

Publications and source records attributed to M Pagano.

At least 217 records · Page 12Linked to original sources
PubMed1983

Cis-platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with curative potential only in women with small tumor burdens.

Thirty-eight women with advanced ovarian cancer were given monthly cycles of intravenous cyclophosphamide, Adriamycin (doxorubicin) and cis-platin, and oral hexamethylmelamine. Of 26 with tumor which would be evaluated for response, 42% had complete remission and 50% partial remission. Median time to disease progression from entry for all 38 patients was 13 months, and median survival 23.5 months. The bulk of tumor at the time chemotherapy was begun was the only significant prognostic factor for time to disease progression and survival. Of the seven women surviving free of disease a median of three years later, five had no mass greater than 2 centimeters in diameter at entry. Toxicity was predominantly myelosuppression and vomiting, with mild peripheral neuropathy in 27% and no significant renal or cardiac toxicity. The response rate of 92% is much higher than that previously reported with melphalan, and the survival considerably longer. The toxicity is acceptable, given the substantial improvement in results.

Adult↗
PubMed1983

Combined modality treatment of regional small cell undifferentiated carcinoma of the lung: a cooperative study of the RTOG and ECOG.

Between 1975 and 1979, 271 patients with regional small cell undifferentiated (including oat cell) carcinoma of the lung were entered into a study involving treatment by radiation therapy (4500 cGy (rad) in five weeks) to the primary tumor, mediastinum and supraclavicular lymph nodes, and a randomization to receive or not receive prophylactic treatment of the brain (3000 cGy in two weeks) and a randomization to prophylactic or delayed chemotherapy (cyclophosphamide and CCNU). Analysis of the data indicates that the median survival for responders (53 weeks) was significantly longer than that of the non-responders and partial responders (37 and 34 weeks). Median survival by treatment arm was 48 weeks for thoracic irradiation (TI), brain irradiation (BI), and early chemotherapy (CT), 44 weeks for TI alone, 41 weeks for TI and CT, 38 weeks for TI and BI. Regional complete and partial tumor responses were 52 and 25% for prophylactic chemotherapy and 44 and 35% for delayed chemotherapy. The site of first failure was regional in 12%, regional and distant simultaneously in 21%, and distant only in 46%. Elective brain irradiation significantly reduced the incidence of brain metastases from 21 and 5%, but did not improve survival.

Brain Neoplasms↗
PubMed1983

[In vitro anti-fungal activity of the econazole-ornidazole combination (1:10 ratio)].

The antifungal activity of Econazole-Ornidazole combination (ratio 1:10) has been evaluated against 90 strains of Candida spp. recently isolated from a clinical environment. Minimal Inhibitory Concentrations (MICs) has been determined by a dilution broth method in test tube with Mycophil Broth (B.B.L) at pH 7.00 and drug concentrations ranging from 800 micrograms/ml to 0.2 microgram/ml. By the same technics it has been determined the pH influence of growth medium, human serum and fungal inoculum on the activity of the association towards the three strains of Candida spp.: C. albicans, C. krusei and C. tropicalis. The obtained data have shown that the Econazole-Ornidazole combination actuates a sure synergic effect towards the tested Candida strains. Such synergism is met at pH 8.00. The plasma proteins influence negatively the antifungal activity of the association proportionally to the increase of the concentration. The same thing happens with the inoculum of yeast. However, this decrease of activity of the association is always smaller than the one found in the compounds alone.

Antifungal Agents↗
PubMed1982

Corrected group prognostic curves and summary statistics.

A method is presented for correcting distribution function estimators for distortions in the joint distribution of covariates in the subsamples receiving different treatments. This form of standardization is useful for depicting multivariate analyses and predicting population behavior. Furthermore, it also proves useful for comparing two trials which differ in patient mix and for adjusting estimates for know imbalances in patient characteristics. Standardization though important, is not often used in clinical trials because of the complexities introduced by multiple covariates. The proposed method overcomes these difficulties in a wide class of analyses.

Age Factors↗
PubMed1982

Inhibition of cathepsin L and B by haptoglobin, the haptoglobin-hemoglobin complex, and asialohaptoglobin. "In vitro" studies in the rat.

In broadening our research on the inhibition of cathepsin B (EC 3.4.22.1) by rat haptoglobin, we have used the haptoglobin-hemoglobin complex and asialohaptoglobin. The inhibition of cathepsin L (EC 3.4.22.15), another lysosomal thiol proteinase, by haptoglobin and its related molecules has also been investigated. With azocasein as substrate, both enzymes were inhibited by both haptoglobin and its related molecules. When azocasein was used as a substrate, the apparent Michaelis constant (Km, app.) for cathepsin L was 1 X 10(-5) +/- 0.4 X 10(-5) M. When haptoglobin was added, the apparent inhibition constant (Ki, app) was 3 X 10(-8) +/- 2.5 X 10(-8) M. The results suggest that rat haptoglobin specifically inhibits lysosomal thiol proteinases and that it has a regulatory role in tissue proteolysis associated with the inflammatory reaction. On the other hand, these properties would seem to be peculiar to the systems rat haptoglobin-rat liver cathepsin B or L.

Animals↗
PubMed1982

Hexamethylmelamine and cisplatin in advanced ovarian cancer after failure of alkylating-agent therapy.

Thirty-eight women with advanced ovarian cancer resistant to alkylating-agent chemotherapy were treated with a combination of hexamethylmelamine and cisplatin. Hematologic toxicity was severe or life-threatening in seven of 13 patients treated with cisplatin at a dose of 100 mg/m2 but was acceptable in 25 patients treated at 75 mg/m2. Thirty-four percent of the combined group developed peripheral neuropathy and only 8% of those treated at 75 mg/m2 developed transient azotemia. Nine complete responses and 12 partial remissions were noted among 38 patients treated, with no obvious advantage for the higher dose of cisplatin. The median duration of remission was 8 months and the overall median survival was 9 months. The response rate of 55% is approximately twice that reported with either agent given alone in similar patient populations and is equal to or better than that reported for more complicated regimens containing these drugs together with other, less active drugs.

Adenocarcinoma↗
PubMed1981

[Multicenter study on the distribution of Streptococcus pneumoniae strains in Italy].

Pneumococcal serotyping by quellung reaction has been performed in five Italian areas on 267 strains, isolated from throat swab, sputum, blood, liquor, etc. 37 serotypes have been identified. The most frequent types resulted 19, 6, 3, 20, 9, 4 (in 50% of total samples), with no difference from those detected in other European countries. The proportion of type 19 was the highest among all age group, in four out of five different areas and in bacteremic pneumonia and meningitis. 36 strains were isolated from infection sites among which type 19 resulted more frequent than in isolates from throat swab and sputum (27.7% versus 16.1%). Pneumococcal serotyping should be routinely done in the light of forthcoming use of polysaccharide vaccine.

Adult↗
PubMed1980

Kinetic study of the interaction between rat haptoglobin and rat liver cathepsin B.

One of the roles of the acute phase reactants (APR), according to Koj, is to regulate the action of tissue proteinases released during the inflammatory reaction. To study this phenomenon in vitro, rat liver cathepsin B (EC 3.4.22.1), a lysosomal proteinase, and a typical APR, rat serum haptoglobin, were purified. By kinetic study, haptoglobin was found to inhibit cathepsin B and the inhibitory activity of a competitive type was increased with the molecular weight of the substrate. When 125I-labelled denatured bovine serum albumin (BSA) was used as a substrate, the apparent Michaelis constant (Km app.) for cathepsin B was 5 +/- 0.4 X 10(-6) M. When haptoglobin was added, the apparent inhibition constant (Ki app.) was 3.5 +/- 1.5 X 10(-8) M. Native haptoglobin was not catabolized by cathepsin B while under the same conditions denatured haptoglobin was degraded by the enzyme.

Animals↗
PubMed1980

Hypothalamic amenorrhea in runners of normal body composition.

Three amenorrheic runners of normal body weight, in whom organic disease had been excluded, were found to exhibit: (1) normal body composition, (2) low baseline concentrations of serum LH and normal concentrations of FSH, (3) normal to hyper-responsiveness of LH and FSH to GnRH testing, and (4) normal and possibly increased frequency of LH pulsations. In one of the 3 runners, the administration of naloxone was followed by a pronounced increase in the amplitude of the LH pulsations.

Adolescent↗
PubMed1980

Combination chemotherapy of advanced ovarian cancer with hexamethylmelamine, cis-Platinum, and doxorubicin after failure of prior therapy.

Forty-nine women received a combination of cis-platinum and hexamethylmelamine (36 also received doxorubicin) for advanced ovarian cancer progressing after therapy that included an alkylating agent or extended field radiation. Twenty-six (53%) had an objective remission that lasted a median of 6 months from start of treatment. Response rate was independent of age, extent of prior therapy, and performance status. A long interval from initial diagnosis to entry, response to therapy, and ambulatory performance predicted improved survival from entry. No patient is surviving free of disease. Myelosuppression and vomiting were moderately severe but tolerable. Azotemia and peripheral neuropathy were infrequent and milk. These drugs have major activity in this poor-risk group and should be studied as part of initial therapy when enhanced efficacy and reduced toxicity are to be expected.

Adult↗
PubMed1979

The application of robust calibration to radioimmunoassay.

The minute concentrations of many biochemically and clinically important substances are currently estimated by radioimmunoassay (RIA). Traditionally, the most popular approaches to the statistical analysis of RIA data have been to linearize the data through transformation and fit the calibration curve using least squares or to directly fit a nonlinear calibration curve using least squares. Estimates of the hormone concentration in patients are then obtained using this curve. Unfortunately, the transformation is frequently unsuccessful in linearizing the data. Furthermore, the least squares fit can lead to erroneous results in both approaches since the many sources of error which exist in the RIA process often result in outlier observations. In this paper, an approach to the analysis of RIA data which incorporates robust estimation methods is described. An algorithm is presented for obtaining the M-estimates of nonlinear calibration curves. The curves to be fitted are modified hyperbolae based on 12 to 16 observations. A procedure, based on the application of the Bonferroni Inequality, is presented for obtaining tolerance-like interval estimates of the concentration of the hormone of interest in the patients. Results of simulations are cited to support the method of construction of confidence bands for the fitted calibration curve. Data obtained from the Veteran's Hospital, Buffalo, New York are used to illustrate the application of the algorithm which is presented.

Calibration↗
PubMedDate not supplied

Studies of AIDS and HIV surveillance. Screening tests: can we get more by doing less?

Estimating the prevalence of the human immunodeficiency virus (HIV) in a group is challenging; this is especially so when the prevalence is small. One reason is that the presence of measurement errors resulting from the limited precision of tests makes estimation, using traditional methods, impossible in some screening situations. Measurement error is real, ignoring it leads to severe bias, and inference about the prevalence becomes unsatisfactory. Indeed, in a low prevalence situation the expected number of false positives is very high, often even higher than the number of true positives. The second reason is that in the low prevalence areas the large sample is needed in order to obtain non-zero estimate. This is usually a very costly, and often unrealistic, solution. This paper considers the advantages and disadvantages of pooled testing as an alternative solution to this problem. We show that by pooling sera samples we not only achieve a cost saving but also, which is counterintuitive, an increase in the estimation accuracy. We also discuss the statistical issues associated with the resulting estimator.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

The effect of covariates on the induction time of AIDS using improved imputation of exact seroconversion times.

This paper explores the effects of covariates such as age, gender, chronological time of seroconversion, and mode of virus transmission on the interval between HIV seroconversion and the development of AIDS. For many cohorts which are available to provide information about such effects, both the time of seroconversion and the time of onset of AIDS may be right- or interval-censored. To analyse these doubly-censored data, we propose a method in which we first estimate the marginal distribution of the chronological time of seroconversion and use this distribution to impute the seroconversion time for each subject. Subsequently, we estimate the distribution of induction times conditional on the seroconversion distribution. We apply this technique to a cohort of HIV seropositive subjects recruited from various outpatient facilities throughout Italy and show that age at seroconversion has the greatest effect on induction time.

Acquired Immunodeficiency Syndrome↗