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Biomedical subjects

A Clerico

Publications and source records attributed to A Clerico.

At least 163 records · Page 9Linked to original sources

Ten-day schedule oral etoposide therapy in advanced childhood malignancies.

PURPOSE: The activity of etoposide (VP-16) has been demonstrated to be schedule-dependent. Several studies have been conducted on the efficacy and safety of different schedules of VP-16 both in adults and in children, but the optimal schedule has not been determined. METHODS: In the current study, the feasibility and effectiveness of prolonged oral VP-16 in children with high-risk malignancies were evaluated. Between April 1995 and February 1999, 15 pretreated patients with high-risk tumors received oral VP-16. The schedule of therapy was oral VP-16 50 mg/m2/day for 10 consecutive days and 1-week interval between cycles. Therapy was stopped after 1 year of treatment or at time of progressive disease or possible surgery. All patients had received parenteral VP-16 in their earlier chemotherapy. RESULTS: Twelve patients were evaluable for tumor response. After 2 to 4 months of treatment, one patient had complete remission (CR), two had partial response (PR), two had minor response (MR), two had mixed response (MxR), three had stable disease (SD), and two had progressive disease (PD). A useful palliative effect was noted in patients with stable disease. In three patients, oral VP-16 was administered for maintenance therapy. After an average follow-up of 27.5 months (range, 7-41 months), five patients are alive without disease (in three, total surgery was performed after VP-16 therapy) and three patients are alive with disease. Six patients died of progressive disease, and one died of promyelocytic leukemia. One patient had Grade 34 thrombocytopenia; in the remaining patients, no acute toxicity was observed during treatment. CONCLUSIONS: This schedule of oral VP-16 produced CRs, PRs, and MRs in medulloblastoma, neuroblastoma, teratocarcinoma, and ependymoma. Stable disease was observed in three patients, one with an Askin tumor, one with medulloblastoma, and one with hepatoblastoma. Given the possible leukemogenic risk, this schedule should be used as a palliative form of therapy or in patients with poor prognosis..

Administration, Oral↗

External quality assurance of the carcinoembryonic antigen (CEA) assay: main findings in six years' experience.

In 1984 we initiated a national external quality assessment (EQA) program (supported by the Italian National Research Council, CNR) for the CEA assay; at present, about 200 Italian laboratories are participating in the program. The laboratories assayed the quality control (QC) samples according to their routine procedures and returned the results together with the name of the method/kit they used. The collected results were computer-processed and reports were sent back to the participants. A significant reduction of the CVt (mean between-laboratory agreement) of the CEA assay was observed throughout the EQA survey (from 35% in 1985 to 20-25% in the last cycles). In order to better clarify the differences in variability observed in the first QC cycles against the last ones, we used the ANOVA technique to evaluate the components of variability. The improvement in between-laboratory agreement was mainly due to the reduction of the between-kit component (from 30.5% to 15.2%), rather than to the smaller decrease observed for the within-kit variability (from 18.4% to 14.0%). The results reported for QC samples from different materials showed differences in the between-lab variability and substantial changes of the kit biases, thus suggesting a different specificity of the antibodies used in the various method/kits against different families of CEA molecules. Considerable uncertainty was also encountered in the clinical classification of low pathological samples, which seems mainly due to the variability in cut-off values used by the laboratories for the clinical assessment of the same analytical results. Our data indicate a progressive increase in the reliability of CEA determination during our study and confirm that EQA has improved the reliability of analysis carried out by the participating laboratories, thus stimulating the kit manufacturers to provide more reliable products.

Antibody Specificity↗

[An exceptional case of hypersensitivity to actinomycin D. Case report and review of the literature].

We report the first case, to our knowledge, of an allergic attack following the administration of Act-D in a 9 year old boy, affected by orbit embrional rabdomyosarcoma. The boy was given most operative therapy according to RMS 96 protocol, IRS group IIb, with Actinomicin D (Act-D), Vincristine and Ifosfamide and RT. Immediately after the beginning of chemotherapy the boy presented with an asthma-like attack (dyspnoea and asthenia), supposed to be a side effect of Ifosfamide administration regressed by intravenous bolus of hydrocortisone and chlorphenamine. In the second chemotherapy cycle concurrent with RT, the Act-D preceded the administration of ifosfamide. Subsequently to the administration of Act-D and RT, without premedication, the boy presented with a face erythema and asthma like attach. Post operative chemotherapy was achieved with no further allergic side effect using premedication with hydrocortisone and chlorphenamine. The boy is now 13 years old, alive and disease free at a three years follow-up.

Antibiotics, Antineoplastic↗

Endogenous digitalis-like factors (EDLF) in obese individuals: preliminary results.

We measured by RIA the serum and urinary digoxin-like immunoreactivity (EDLF) in 8 subjects with severe obesity and in 10 healthy, non-obese individuals (as a control group), to evidentiate whether circulating and urinary levels of EDLF are increased in obesity. For each individual, we measured the mean EDLF on two sera collected consecutively on two successive mornings, between 8-9 a.m. and the daily urinary EDLF excretion. Every subject collected his/her 24 hour urine in 5 different timed fractions. For each urine fraction, we measured the excretion of EDLF, electrolytes (Na and K), and creatinine. In obese people, the mean serum digoxin-like immunoreactivity (no. 8, 27.3 +/- 8.7 ng/L de) was significantly higher (unpaired t test, p = 0.0002) than in the controls (no. 10, 12.0 +/- 7.3 ng/L de), whereas control and obese subjects had superimposable 24 hour EDLF urinary excretion. Urinary excretion of EDLF significantly changed throughout the day in normals, but not in obese people. In a multiple stepwise regression analysis, urinary K+ and Na+ significantly (p less than 0.01) contributed to the regression with urinary EDLF (EDLF = 76.9 + 0.67 K+ - 0.24 Na+; R = 0.601, no. 40) in obese individuals. The in vivo kinetic and metabolic pathways of EDLF are conceivably different in obese and normal subjects. A difference in the production rate, binding to plasma proteins and/or removal mechanisms could explain the findings of higher circulating levels with normal EDLF urinary excretion in obese persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Administration of GSH has no influence on the RBC membrane: oxidative damage to patients on hemodialysis.

In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt.

Adult↗

Evaluation and comparison of the analytical performances of two RIA kits for the assay of atrial natriuretic peptides (ANP).

We evaluated the analytical performance of two commercial RIA kits for the assay of plasma atrial natriuretic peptide (ANP), which use different antisera and tracers, in order to verify the most suitable RIA procedure for the assay of ANP in plasma samples. In particular, two different procedures for the purification of plasma were evaluated. The first one uses the extraction of plasma samples with Sep-Pack C18 cartridges and the second immunoextraction (C-terminal ANP-specific antibody bound to solid phase of Sepharose). The sensitivity and precision of the two RIA kits proved inadequate, being unable to provide an acceptably precise measurement of the plasma ANP concentrations in normal subjects. An improvement in precision and sensitivity was obtained by using "fresh" (or purified) preparations of the tracer and standard solutions, and by adding PEG to the B/F separation step. The direct assay (without preliminary purification) was not possible due to a serious overestimation of plasma levels due to the presence of interferences; on the other hand, the extraction step increased the imprecision and the complexity of the assay. Moreover, the extraction recovery of ANP added to plasma samples in the procedure using Sep-Pak cartridges is about 50-60%, while it was found to be almost complete (about 90%) in the immunoextraction procedure. Moreover, a comparison of the results obtained with the two RIA systems indicated that the antisera have comparable sensitivities, but quite different specificities; however, neither of the two RIA kits showed a completely satisfactory degree of sensitivity, precision and practicability.

Atrial Natriuretic Factor↗

Radioreceptor assay for the measurement of endogenous digitalis-like factors using membrane particulate fraction of human placenta and 125I-digoxin: comparison with RIA method.

We measured purified extracts of serum (plasma) or urine samples of newborns, pregnant women, normal adults, and uremic patients by a radioreceptor assay (RRA), which uses particulate membrane fractions from human placenta as a binding system, and 125I-digoxin as a tracer. We also measured the digoxin-like immunoreactivity by a sensitive RIA, and results were compared with those found by the RRA. Specific 125I-digoxin binding to placental receptors was competitively inhibited by purified plasma and/or urine extracts of newborns, adult subjects, pregnant women and uremic patients. A linear relationship was found between inhibition of binding and volume of plasma and urine assayed. Moreover, a significant correlation was found between the values obtained by RRA and those found by RIA (n = 17, r = 0.699, p = 0.0012). Our data confirm that increased circulating and/or urinary levels of substances with biological and immunological activity similar to cardiac glycoside drugs are present in newborns, pregnant women and uremic patients compared to healthy adult subjects. In addition, our preliminary study indicates that these endogenous factors are able to bind to the specific receptor of digitalis drugs on the placental membranes.

Adult↗

External quality control survey for alpha-fetoprotein assay.

Starting from 1984 we organized an interlaboratory quality control (QC) survey for the tumor marker AFP in which 100-150 laboratories have been involved. Seven consecutive QC cycles have been carried out during the period 1984-1988; 15-20 samples have been prepared and sent in each cycle. The 11 kits more used in the survey, which use three different immunological methods (3 kits EIA, 3 kits RIA, and 5 kits IRMA) were evaluated. Since the results of AFP assays were expressed as ng/ml of different local standards of the various kits, the participants were asked to convert their results in UI/ml of the 1st IRP 72/225 distributed by WHO. The total variability of AFP assay resulted approximately constant (19.9-24.7 CV%) during the all QC period. The validity of the consensus mean of AFP determinations obtained in the survey and assumed as reference value has been checked by recovery experiments. Regression analysis indicates that the consensus means found in these samples are in very good agreement with the added AFP. The analytical performance achieved by the most popular methods/kits, observed in the last period, are also reported.

Italy↗

Measurement of urinary albumin excretion (UAE) in diabetic patients: immunonephelometry versus radioimmunoassay.

We have compared the chemico-clinical characteristics of an immuno-nephelometric technique (INA) with those of a solid-phase radioimmunoassay (RIA) method for the measurement of urinary albumin excretion (UAE) in diabetic patients. The UAE was evaluated in 227 diabetics; all, except 9, were Albustix-negative. The calibration of the nephelometer apparatus every time before the assay did significantly improve the accuracy and precision of the INA method. Similar values were obtained with the two methods (INA = 2.1 + 0.95 RIA, n = 227, r = 0.969) through all the ranges of albumin concentration explored. INA seems as suitable as RIA for the assay of UAE in diabetics. The two methods are comparably accurate and precise. However, RIA appears more sensitive than INA, while immunonephelometric system is easier and faster to perform (up to 200 samples can be assayed in about 1 hour, while 2-4 hours are necessary with RIA), with fewer handling steps. The INA instrumentation is automated and the reagents are more stable and less hazardous than those used in RIA. However, due to the cost of the nephelometer apparatus, the INA technique may be employed by those laboratories which have already this instrumentation or by those which will use it in the next future for the assay of other analytes in addition to albumin.

Albuminuria↗