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Biomedical subjects

D Natale

Publications and source records attributed to D Natale.

At least 19 recordsLinked to original sources

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.

Adenocarcinoma↗

Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients: a Southern Italy Cooperative Oncology Group phase II study.

Oxaliplatin 100 mg/m(2) iv on day 1, and capecitabine 1,000 mg/m(2) orally bid from day 1 (evening) to day 11 (morning) were administered every 2 weeks (OXXEL regimen) to 38 patients as first-line treatment for metastatic colorectal carcinoma. A total of 318 cycles were administered, with a median of 8 (range, 4-12) cycles per patient. Response rate (RR) was 45% (95% confidence interval (CI), 29%-62%), with 7 complete responses and 10 partial responses; furthermore, 12 patients showed a stable disease, so that a disease control was achieved in 29 (76%) patients. RR was greater among patients with performance status 0 (52%), without weight loss (52%), younger than 65 years (50%), and previously unexposed to adjuvant chemotherapy (48%), while no correlation was found with the actually delivered oxaliplatin dose intensity. Overall, haematological side effects were negligible, with no case of grade 4 toxicity, and only one patient suffering from an episode of grade 3 neutropenic fever. Severe anaemia occurred in 4 (11%) patients, and grade 3 neuropathy affected 9 (24%) patients. Median progression-free survival was 7.9 (95% CI, 6.2-9.6) months, and median overall survival has not been reached yet. In conclusion, the OXXEL regimen resulted safe and active, and it deserves further evaluation in metastatic colorectal cancer patients.

Adult↗

Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial.

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.

Adult↗

Response of female Cydia molesta (Lepidoptera: Tortricidae) to plant derived volatiles.

Peach shoot volatiles were attractive to mated female oriental fruit moth, Cydia molesta (Busck), in a dual choice arena. No preference was observed between leaf odours from the principle host plant, peach, and the secondary host plant, apple. Twenty-two compounds were identified in headspace volatiles of peach shoots using gas chromatography-mass spectrometry. Green leaf volatiles accounted for more than 50% of the total emitted volatiles. A bioassay-assisted fractionation using different sorbent polymers indicated an attractant effect of compounds with a chain length of 6-8 carbon atoms. The major compounds of this fraction were tested either singly or in combinations for behavioural response of females. Significant bioactivity was found for a three-component mixture of (Z)-3-hexen-1-yl acetate, (Z)-3-hexen-1-ol and benzaldehyde in a 4:1:1 ratio. This synthetic mixture elicited a similar attractant effect as the full natural blend from peach shoots as well as the bioactive fraction.

Animals↗

An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: results from a randomized trial.

STUDY OBJECTIVE: Conventional emergency department testing strategies for patients with chest pain often do not provide unequivocal diagnosis of acute coronary syndromes. This study was conducted to determine whether the routine use of single photon emission computed tomography (SPECT) imaging at rest and early exercise stress testing to assess intermediate-risk patients with chest pain and no ECG evidence of acute ischemia will lead to earlier discharges, more discriminate use of coronary angiography, and an overall reduction in average costs of care with no adverse clinical outcomes. METHODS: All patients in this study had technetium 99m tetrofosmin SPECT imaging at rest and were randomly assigned to either a conventional (results of the imaging test blinded to the physician) or perfusion imaging-guided (results of the imaging test unblinded to the physician) strategy. Patients in the conventional arm were treated at their physician's discretion. Patients in the perfusion imaging-guided arm were treated according to a predefined protocol based on SPECT imaging test results: coronary angiography after a positive scan result and exercise treadmill testing after a negative scan result. Study endpoints consisted of total in-hospital costs and length of stay. Hospital costs were calculated using hospital department-specific Medicare cost/charge ratios. Length of stay was calculated as total hospital room days billed (regular and intensive care). RESULTS: We enrolled 46 patients, 9 with acute myocardial infarctions. Patients randomly assigned to the perfusion imaging-guided arm had $1,843 (95% confidence interval [CI] $431 to $6,171) lower median in-hospital costs and 2.0-day (95% CI 1.0 to 3.0 days) shorter median lengths of stay but similar rates of in-hospital and 30-day follow up events as patients in the conventional arm. CONCLUSION: An ED chest pain diagnostic strategy incorporating acute resting (99m)Tc tetrofosmin SPECT imaging and early exercise stress testing may lead to reduced in-hospital costs and decreased length of stay for patients with acute chest pain and nondiagnostic ECGs.

Aged↗

Impact of bovine oocyte maturation media on oocyte transcript levels, blastocyst development, cell number, and apoptosis.

The objectives were 1) to investigate the effects of oocyte maturation in serum-free and amino acid-supplemented defined media on oocyte transcript levels, blastocyst cell number, and apoptosis; 2) to investigate the influence of oocyte maturation culture atmosphere on blastocyst development, total cell number, and apoptosis; and 3) to examine the influence of epidermal growth factor (EGF) during oocyte maturation on blastocyst cell number and apoptosis. The results demonstrate that blastocysts derived from in vitro maturation, fertilization, and embryo culture protocols undergo apoptosis but that apoptotic levels are not greatly influenced by the oocyte maturation environment. Amino acid supplementation of oocyte maturation media was associated with enhanced developmental frequencies, increased blastocyst cell number, and elevated oocyte maternal mRNA levels. Oocyte maturation with supplemented synthetic oviduct fluid medium (cSOFMaa) resulted in blastocyst cell numbers comparable to those observed with Tissue Culture Medium 199 + newborn calf serum. Blastocyst development was reduced following oocyte maturation under a 5% CO(2), 7% O(2), 88% N(2) culture atmosphere. EGF supplementation of oocyte maturation medium resulted in a concentration-dependent increase in blastocyst development but did not influence blastocyst total cell number or apoptosis. Our findings indicate that cSOFMaa medium is an effective base medium for bovine oocyte maturation.

Amino Acids↗

Evaluation of an agonist index: affinity ratio for compounds active on muscarinic cholinergic M2 receptors.

A protocol for predicting full agonist, partial agonist, and antagonist profiles of compounds with M2 muscarinic cholinergic receptor activity was developed using radioligand binding assay techniques with [3H]-N-methyl scopolamine (NMS) and [3H]-Oxotremorine-M (Oxo-M) as radioligands. Full muscarinic cholinergic receptor agonists such as muscarine and oxotremorine-M expressed a high agonist index (> 3000 for M1 muscarinic cholinergic receptors and > 900 for M2 muscarinic cholinergic receptor), whereas muscarinic receptor antagonists (selective or non-selective) for different receptor subtypes gave a low (0.5-10) agonist index. Functional studies performed on preparations of guinea-pig ileum and heart were consistent with radioligand binding assay experiments. The above results suggest that similarly as already established for the M1 muscarinic cholinergic receptor subtype, evaluation of the [3H]-NMS/[3H]-Oxo-M ratio may provide useful information on the profile of compounds acting at the M2 muscarinic cholinergic receptor subtype. The availability of simple and predictive techniques for the characterization of muscarinic M2 cholinergic receptor agonists, may help the identification of new compounds in therapeutic areas in which stimulation or inhibition of this receptor is desirable.

Animals↗

Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions.

Left ventricular (LV) ejection fraction (EF) is commonly assessed by equilibrium radionuclide angiography and echocardiography. These methods are presumed to be interchangeable for this purpose. This study (1) compares quantification of LVEF by equilibrium radionuclide angiography with visual estimation of LVEF by echocardiography, (2) determines the reproducibility of both methods, and (3) evaluates whether differences in determinations of LVEF are of clinical relevance. Seventy-three clinically stable patients had both equilibrium radionuclide angiography and echocardiography performed within a 4-day period. LVEF by both techniques was compared after blinded analysis by 3 echocardiographers and 3 nuclear technologists. Reproducibility was assessed by blinded repeat analysis after a 1-week interval. The frequency of differences in repeat assessments of EF that the authors considered to be of potential clinical relevance (i.e., difference > or = 10% EF units) was assessed for both techniques. Correlation of LVEF determined by both methods was good (r = 0.81, SEE = 3.5) but with substantial differences in individual patients (limits of agreement, 23.6%). Intra- and inter-observer reproducibility was good for both methods, but better for radionuclide LVEF than for echocardiographic LVEF. Limits of agreement were substantially better for radionuclide LVEF than for echocardiographic LVEF (1.8% to 3.6% versus 13.4% to 17.4%, respectively). Clinically relevant differences did not occur on repeat processing of equilibrium radionuclide angiography. In contrast, potentially clinically relevant differences occurred in 8% to 26% of studies on repeat analysis of echocardiography. Thus, LVEF determined by equilibrium radionuclide angiography and echocardiography show good agreement. Both methods provide clinically valuable measurements for LV function. However, when a precisely reproducible measurement is required for patient management decisions, equilibrium radionuclide angiography is the method of choice.

Adult↗

Quantitative comparison of planar and SPECT normal data files of thallium-201, technetium-99m-sestamibi, technetium-99m-tetrofosmin and technetium-99m-furifosmin.

UNLABELLED: In recent years, several of 99mTc-labeled myocardial perfusion imaging agents have been developed, such as 99mTc-sestamibi, 99mTc-tetrofosmin and 99mTc-furifosmin. Although images obtained with these new tracers have a general similar appearance, there are differences in the myocardial kinetics, body distribution, general quality of images and imaging protocols. The aim of this study was to quantitatively compare normal exercise planar and SPECT data files obtained with 201TI and 99mTc-labeled agents. METHODS: Lower-limit-of-normal curves were generated for each specific radiopharmaceutical from normal subjects with low (< 3%) pretest likelihood of coronary artery disease using circumferential count distribution profiles from planar and SPECT exercise images. Lower-limit-of-normal curves were statistically compared using the nonparametric Kruskall-Wallis and Wilcoxon tests. RESULTS: Planar and SPECT lower-limit-of-normal curves generated for each radiopharmaceutical showed general similarities. Statistically significant differences among the lower-limit-of-normal curves were found in the planar left anterior oblique view and in the planar left lateral view (p < 0.05 for each). No statistically significant differences existed between lower-limit-of-normal curves of various radiopharmaceuticals on the planar anterior view and on SPECT imaging. CONCLUSION: For quantitative analysis of planar images, radiopharmaceutical-specific normal data files are mandatory. Although SPECT normal data files of various radiopharmaceuticals are not statistically different, they are not identical. It appears, nevertheless, prudent to use radiopharmaceutical-specific normal data files for quantitative analysis of SPECT images.

Adult↗

[A case of Reiter syndrome in HIV infection].

The onset of Acquired Immunodeficiency Syndrome (AIDS) is often characterized by a variety of symptoms, with the involvement of several tissues and organs. In the present case a polyarthritic syndrome was the symptomatology at the onset. Clinical onset. A 26 year old man, drug abuser, anti HIV positive, with a CD4/CD8 ratio = 0.8, was observed in January 1990. He presented polyarthritic involvement of the ankles and right knee, conjunctivitis and successfully keratodermia. The diagnosis of Reiter syndrome was made on the basis of the clinical features and laboratory findings (Chlamydia in his urethral secretion). The patient did not denote any symptom of immunodeficiency, except small lymphonodal painless swelling in axillary and latero-cervical region. A significant clinical improvement was obtained with chlortetracycline at a dosage of 100 mg daily and 6 methylprednisolone 12 mg daily. Comment. This experience suggests the importance and the usefulness of the anti HIV test in patients affected by a reactive arthritis, as the Reiter's syndrome, since the progressive diffusion of the HIV infection.

Adult↗

The lack of correlation between the positivity of anti-platelet antibodies and the presence of thrombocytopenia in course of HIV infection.

The presence of anti-platelet autoantibodies has been reported in many cases of HIV infection, but there is no accordance about their pathogenic role in the onset of thrombocytopenia in the patients studied. In the present study surface anti-platelet antibodies (PAIgG) and serum anti-platelet antibodies (sPAIgG) were assayed in a group of 135 HIV-infected patients (109 men, 26 women), in different clinical stages by using an immunofluorescence test (PSIFT). In order to investigate the possible correlation of the positivity of these autoantibodies and the onset of thrombocytopenia, some of these patients were controlled in a follow-up study, with two successful controls: 10 months (II control: 89 patients) and 20 months (III control: 59 patients) after the first time. In the I control PAIgG were positive in 68 subjects (50.4%) and sPAIgG in 34 (25.2%); both PAIgG and sPAIgG were present in 23 patients (17%). 56 patients did not present anti-plt antibodies (41.5%). No significantly different distribution of these autoantibodies in each stage of disease was observed. The mean value of platelet count resulted in the normal range both in the anti-plt antibody positive and in the anti-plt antibody negative patients, but the value found in the anti-plt antibody positive patients was significantly lower than the one found in the anti-plt antibody negative group (p < 0.01). This difference was more marked between the group with PAIgG and anti-plt antibody negative patients than between the group with sPAIgG and the anti-plt antibody negative patients (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Randomized comparison of ceftriaxone versus ceftriaxone plus amikacin for the empirical treatment of infections in patients with altered host defense: microbiological and clinical evaluation.

Two hundred and eighty-four febrile episodes in immunocompromised patients were treated with ceftriaxone alone or in combination with amikacin. In the ceftriaxone-treated group, 60 out of 143 febrile episodes were microbiologically documented, while in the group receiving the combination therapy, there were 32 out of 140 (p = 0.0007). Gram-positive microorganisms were more common than gram-negative ones, accounting for 59 of the 101 isolated bacteria. The ceftriaxone regimen appeared to have a response rate comparable to the combination regimen (73.91 vs. 78.88%). Superinfections occurred under both regimens.

Adult↗

Cytogenetics and bone marrow transplantation.

The authors report hematologic and cytogenetic data on 19 patients treated with allogeneic bone marrow transplantation (BMT) for severe hematologic disorders: 8 patients with chronic myelogenous leukemia, 6 with acute leukemia, 3 with severe aplastic anemia, 1 with refractory anemia, and 1 with beta-thalassemia major. Cytogenetic assays were performed on marrow cells before conditioning, 30 days after BMT, and at subsequent times. The authors discuss the role of cytogenetic studies in the evaluation of bone marrow engraftment, leukemic transformation of the graft, and disease relapse.

Acute Disease↗

Quantitative comparison of single-isotope and dual-isotope stress-rest single-photon emission computed tomographic imaging for reversibility of defects.

BACKGROUND: Dual-isotope rest/stress single-photon emission computed tomographic (SPECT) imaging is a time-saving imaging protocol. However, the stress radiotracer, technetium 99m-labeled sestamibi, and the rest radiotracer, thallium 201, have different physical properties and myocardial kinetics. In patients with abnormal resting myocardial perfusion, these differences may affect quantification of rest defect size and defect reversibility. The purpose of the study was to compare myocardial perfusion defect reversibility quantitatively by single-isotope (rest/stress sestamibi) and dual-isotope (rest thallium/stress sestamibi) SPECT. METHODS AND RESULTS: Thirty patients with prior myocardial infarction underwent rest/stress sestamibi SPECT imaging and rest thallium SPECT imaging. Defects were quantified according to circumferential count profiles with a normal sestamibi database. The images of a subgroup of 21 patients were processed with radiotracer-specific normal databases. Defect size and defect reversibility were compared quantitatively for single-isotope and dual-isotope SPECT. Rest sestamibi defect size was significantly larger than rest thallium defect size (19 +/- 15 vs 14 +/- 16; p = 0.007). Defect reversibility was larger with thallium than with sestamibi (10 +/- 9 vs 6 +/- 6; p = 0.002). With radiotracer-specific normal databases, mean rest sestamibi and thallium defect sizes in 21 patients were not different (23 +/- 19 vs 21 +/- 17; difference not significant). With radiotracer-specific normal databases, mean defect reversibility was not different with either sestamibi or thallium (6 +/- 6 vs 8 +/- 9; difference not significant), although correlation among individual patients was only fair (r2 = 0.48). CONCLUSION: In patients with prior myocardial infarction, stress-induced defect reversibility is quantitatively larger with dual-isotope imaging than with single-isotope imaging. Quantitative processing of dual-isotope images requires radiotracer-specific normal databases. Because of different characteristics of sestamibi and thallium, assessment of defect reversibility on dual-isotope images should be made with caution. Only relatively large defect reversibility can be assumed to represent true stress-induced myocardial ischemia.

Dipyridamole↗