Biomedical subjects

R Natale

Publications and source records attributed to R Natale.

At least 19 recordsLinked to original sources

PubMed2005

Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes.

PURPOSE: Gemcitabine-platinum combination activity has been clearly established in a number of phase II studies. It has also been compared against other combinations in many phase III trials. It is generally believed that all such regimens have an equivalent impact on survival. This meta-analysis aims to quantify the treatment effect of gemcitabine plus a platinum agent in the treatment of advanced NSCLC and compare the combination to other regimens used globally. DESIGN: Data from a total of 4556 patients from 13 randomized trials investigating gemcitabine in combination with a platinum agent versus any other platinum-containing regimen were included in a meta-analysis of time-to-event outcomes. RESULTS: A significant reduction in overall mortality in favor of gemcitabine-platinum regimens was observed, hazard ratio (HR) 0.90 (95% CI: 0.84-0.96) with an absolute benefit at 1 year of 3.9%. Median survival was 9.0 months for the gemcitabine-platinum regimens and 8.2 months for the comparator regimens. Sub-group analysis of the first- and second-generation platinum-based comparator regimens also indicated a significant benefit for gemcitabine-platinum regimens, HR 0.84 (CI: 0.71-0.9985). Analysis of third-generation agent plus platinum regimens showed a non-significant trend favoring gemcitabine-platinum regimens, HR 0.93 (CI: 0.86-1.01). There was a significant decrease in the risk of disease progression in favor of gemcitabine-platinum regimens, HR 0.88 (CI: 0.82-0.93). An absolute benefit of 4.2% at 1 year was estimated. Median progression-free survival was 5.1 months for gemcitabine-platinum regimens compared with 4.4 months for the comparator regimens. Sub-group analysis indicated a statistically significant progression-free survival benefit for patients assigned to gemcitabine-platinum treatment compared to first- and second-generation platinum regimens, HR 0.85 (CI: 0.77-0.94), and third-generation agent plus platinum regimens, HR 0.89 (CI: 0.82-0.96).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

A ten-year review of progress in the treatment of non-small-cell lung cancer with gemcitabine.

During the past two decades, clinical research has focused on developing chemotherapeutic regimens that effectively prolong survival and provide palliation for patients with non-small-cell lung cancer (NSCLC). In the mid-to late-1990s, several new agents emerged from clinical development and demonstrated activity against this disease, including the novel antimetabolite gemcitabine. Gemcitabine is one of the most active agents for the treatment of NSCLC. When combined with a platinum analog, gemcitabine produces the best progression-free survival outcome of any platinum-based regimen in first-line advanced NSCLC treatment setting. On the basis of its excellent antitumor activity and favorable toxicity profile, gemcitabine has been approved for the first-line treatment of locally advanced or metastatic NSCLC.

Antimetabolites, Antineoplastic↗

PubMed2003

Does cervical length at 13-15 weeks' gestation predict preterm delivery in an unselected population?

OBJECTIVE: To assess the role of early mid-trimester cervical length measurement as a predictor of spontaneous preterm birth in an unselected population. METHODS: In this prospective study, unselected, asymptomatic, Caucasian women with singleton pregnancies underwent standardized transvaginal ultrasonographic (TVS) cervical length measurement at 13-15 weeks' gestation as a screening test for preterm delivery (PTD). Women with multiple gestations, iatrogenic PTD, and previous cervical conization were excluded. The primary outcome measures were spontaneous PTD at < 37 and < 34 weeks. The correlation between cervical length and previous obstetric history was evaluated. RESULTS: A total of 2469 patients met the inclusion criteria. The mean gestational age at cervical assessment was 14 + 2 weeks. The mean gestational age at delivery was 40 + 0 weeks. The rate of spontaneous deliveries before 37 weeks' gestation was 1.7%. In 0.2% the delivery occurred before 34 weeks' gestation. The mean +/- standard deviation cervical length for the entire population was 44.2 +/- 5.4 mm. No difference was observed between cervical length in women that delivered at term and those that delivered either before 37 or before 34 weeks' gestation. Previous obstetric history (prior preterm birth, previous miscarriages and terminations, and parity) did not affect cervical length at 14 weeks of gestation. CONCLUSIONS: Performed at 14 weeks' gestation, TVS measurement of the cervical canal length to predict spontaneous PTD is not a reliable screening procedure.

Adolescent↗

PubMed2001

Obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension.

OBJECTIVE: The purpose of this study was to determine the obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension. STUDY DESIGN: Induction and operative delivery rates and indices of maternal and neonatal morbidity were determined in women (37-41 completed weeks) with gestational hypertension (n = 979), preeclampsia (n = 165), chronic hypertension (n = 187), and control subjects (n = 11,434) in a retrospective review of St. Joseph's Health Care Perinatal Database from November 1, 1995, to October 31, 1999. Data were analyzed by chi-square test, analysis of variance, Dunnett's t -test, and pairwise chi-square tests with Bonferroni correction. RESULTS: The induction and cesarean delivery rates in gestational hypertension were similar to preeclampsia and chronic hypertension groups and almost double of control subjects. The length of labor and postpartum stays and the incidence of operative vaginal delivery, postpartum hemorrhage, and neonatal intensive care involvement were greater in the gestational hypertension group than in the control subjects. CONCLUSION: Women with gestational hypertension had obstetrical intervention rates much higher than control subjects and similar to those with preeclampsia and chronic hypertension.

Adult↗

PubMed2001

Antepartal assessment of IUGR fetuses.

Intrauterine growth restriction (IUGR) should be defined on the basis of a prenatally recognized defective growth compared to that expected for this fetus. This condition is encountered in 10-15% of the pregnancies and the perinatal outcome is impaired mainly as a consequence of fetal hypoxemia that is present in 30% of IUGR fetuses. In order to allow for proper management, the IUGR should be recognized prenatally and the method of choice for this purpose is ultrasound fetal biometry. After the identification of IUGR, 2nd level tests should be performed in order to assess the fetal oxygenation conditions. The validity of Doppler investigation on fetal and umbilical vessels is discussed, and the importance of using computer assisted cardiotocography instead of traditional eye ball evaluation of the non-stress test is emphasized.

Cardiotocography↗

PubMed2000

Early screening for fetal cardiac anomalies by transvaginal echocardiography in an unselected population: the role of operator experience.

OBJECTIVES: To examine the accuracy of early transvaginal fetal echocardiography performed in an unselected population by operators with different levels of experience and to compare the results with those obtained from a referral population. DESIGN: Prospective study. METHODS: A series of 4785 unselected fetuses and 221 referred fetuses were screened at 13-15 weeks' gestational age by transvaginal echocardiography. For each fetus, visualization of the four-chamber view plus the origin of the great arteries was attempted. Color Doppler imaging was only performed in cases of cardiac malformations already identified by two-dimensional echocardiography. The scans were performed by seven operators with different levels of experience. Reliability was assessed by conventional transabdominal echocardiography at 20-22 weeks, by postnatal follow-up in the first 3 months of life, and/or by autopsy in all cases of termination or fetal death. RESULTS: The rate of complete visualization (four-chamber view plus great arteries) was 47.5% in the unselected population, and 76.9% in the referral population. There were four (0.08%) true positives among the unselected fetuses, and five (2.3%) among referrals, mostly with enlarged nuchal translucency or other malformations. Among the unselected fetuses, nine false negatives were detected by transabdominal echocardiography. Improvement in the operators' ability to recognize cardiac anomalies in unselected population was disappointing and was influenced more by individual approach than by the number of examinations performed. CONCLUSIONS: Early screening for cardiac anomalies among unselected fetuses is ill-advisable. The usefulness of an early approach is confirmed in high risk fetuses or in the presence of enlarged nuchal translucency when performed by expert operators.

Adult↗

PubMed1999

Technical factors in early amniocentesis predict adverse outcome. Results of the Canadian Early (EA) versus Mid-trimester (MA) Amniocentesis Trial.

The purpose of this study was to identify risk factors for fetal loss and other pregnancy complications associated with genetic amniocentesis. Data were acquired in the Canadian Early Amniocentesis Trial (CEMAT), a multicentered (12) prospective, randomized trial comparing continuous ultrasound-guided early amniocentesis (EA) and mid-trimester amniocentesis (MA) (CEMAT Group, 1998). Details of the procedure were recorded and analysed by allocation (EA versus MA), operator and centre, and correlated with pregnancy outcome. A total of 62 spontaneous pregnancy losses occurred between the procedure and 20 weeks' gestation among the 3691 patients who received their procedures within the allocated window (EA=53/1916, MA=9/1775). Technical factors correlating with these losses included procedures 'judged to be difficult' by the operator, and post-procedure amniotic fluid leakage or bleeding. Maternal risk factors included maternal hypertension (fetal loss 11. 1 per cent, compared with non-hypertensive women, 2.6 per cent) increased body mass index (BMI) and gravidity of three or greater. Allocation to EA was predictive of fetal loss, as well as failed procedure, multiple needle insertions, amniotic fluid leakage, failed culture and talipes equinovarus, in excess compared with MA. In conclusion, in this large prospective randomized trial evaluating amniocentesis, specific maternal, fetal and procedural variables were found to be predictive of fetal loss and adverse pregnancy outcome. Performing amniocentesis before 13 weeks' gestation (EA) was the major predictive factor for adverse outcome. These data suggest that first-trimester chorionic villus sampling (CVS) and MA will likely remain the invasive procedures of choice for evaluation of fetal karyotype.

Abortion, Spontaneous↗

PubMed1999

An endodermal sinus tumor diagnosed in pregnancy: case report and review of the literature.

OBJECTIVE: The use of chemotherapeutic drugs in pregnancy is a rare occurrence. Experience and results need to be shared. METHOD: At 23 weeks gestational age, a patient was diagnosed with an endodermal sinus tumor of the ovary. She received one course of postoperative bleomycin, cisplatin, and etoposide. One week later, the patient was investigated for increasing abdominal pain and the fetus was noted to have ventriculomegaly. RESULTS: The baby was delivered, and the patient was surgically staged and completed chemotherapy. Although the patient is alive and well 16 months after delivery, the infant has developed significant ventriculomegaly with cerebral atrophy. CONCLUSION: The etiology of this infant's significant cerebral atrophy is not clear. Tumor-specific, perioperative, or drug-related events must be considered.

Adult↗

PubMed1998

Comparisons of first and second trimester screening for fetal anomalies.

Four thousand fifty unselected pregnant women bearing a total of 4,078 fetuses were examined by transvaginal sonography (TVS) at 14 weeks of gestational age and rescreened via transabdominal sonography (TAS) at 21 weeks. Fifty-four of 88 anomalies were correctly identified at first scan whereas 34 were not; of these, 24 were discovered at second trimester rescreening, and the remaining 10 were observed later in pregnancy or after birth. The sensitivity of TVS screening with respect to final outcome was 61.4% (54 of 88 malformations in total) and 69.2% in comparison to TAS screening results (54 malformations detected among 78 recognized within 21 weeks). The association between fetal malformation and chromosomal aberrations was also investigated: in our study population there were 21 aneuploidies, 14 of which were recognized because of abnormal findings at the 14 weeks' TVS, 5 at the TAS rescreening, and 2 after birth in neonates free of structural abnormalities.

Chromosome Aberrations↗

PubMed1998

Fetal oxygen saturation and fractional extraction at birth and the relationship to measures of acidosis.

OBJECTIVE: We sought to determine umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population and their predictive value for measures of acidosis. STUDY DESIGN: The computerized perinatal database of St. Joseph's Health Centre, London, Ontario, was used to obtain the umbilical cord gases, pH, mode of delivery, gestational age at delivery, and nuchal cord status for all live-born infants >500 gm between January 1991 and December 1995 (n = 22,134). Oxygen saturation values were calculated from the umbilical cord PO2 and pH data with a previously derived empirical equation, the accuracy of which was rechecked with 100 consecutive cord blood samples where oxygen saturation values were both calculated and measured with a hemoximeter (r = 0.99, p = 0.001). Fractional oxygen extraction values were calculated from the umbilical cord oxygen saturation data. RESULTS: There were 18,250 "validated" paired umbilical vein and artery blood gas and pH results available for analysis after patient case exclusions for missing, unreliable, or "unphysiologic" data. For all validated patient cases, mean umbilical vein oxygen saturation was 63% +/- 16% (SD), mean umbilical artery oxygen saturation was 24% +/- 15%, and mean fractional oxygen extraction was 0.62 +/- 0.20, with all three of these parameters significantly affected by mode of delivery, gestational age at delivery, and nuchal cord status. Umbilical vein and artery oxygen saturation and fractional oxygen extraction values showed significant relationships with umbilical artery base excess, albeit weak (r = 0.18 to 0.22), and pH (r = 0.46), which were best described using cubic regression models. Receiver-operator characteristic curve statistics for the prediction of acidosis at birth were also significant for all three of these parameters but lower when predicting metabolic versus mixed acidosis. However, all showed a poor positive predictive value for significant acidosis at birth, whether metabolic or mixed and regardless of the cutoff values used. CONCLUSION: Umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population indicate a decreased oxygen margin of safety for infants born postterm, by cesarean section after labor, and with a nuchal cord. However, these values have a limited relationship to measures of acidosis, which may have clinical implications for the usefulness of intrapartum pulse oximetry.

Acidosis↗

PubMed1997

Prediction of umbilical artery base excess by intrapartum fetal oxygen saturation monitoring.

OBJECTIVE: Our purpose was to evaluate the predictive value of intrapartum fetal oxygen saturation as monitored by reflectance pulse oximetry (SpO2) for metabolic acidosis at birth. STUDY DESIGN: An observational study was carried out on intrapartum patients at > or = 35 weeks' gestation having either a nonreassuring fetal heart rate pattern, intrauterine growth restriction, or thick meconium. Fetal oxygen saturation monitoring was performed with use of the Nellcor N-400 monitor and the FS-14 fetal oxygen sensor. Mean values of SpO2 from the last 30 minutes of monitoring were correlated with umbilical artery base excess and pH at birth, with use of regression analysis, whereas the prediction of acidosis by SpO2 at different thresholds was tested with use of receiver-operator characteristic curve calculations. RESULTS: Fifty-four patients met the criteria for data analysis, with a mean SpO2 monitoring time of 150 +/- 124 minutes (SD) and a mean signal loss of 30% +/- 20%. Mean fetal SpO2 for the last 30 minutes of monitoring averaged 42.1% +/- 9.9% and, for individual patient studies, correlated significantly with calculated oxygen saturation in the umbilical vein (r = 0.52, p < 0.001) and in the umbilical artery (r = 0.34, p = 0.02) as measured at birth. However, the correlation with umbilical artery base excess values at birth was somewhat weaker (r = 0.30, p < 0.05), as was the correlation with umbilical artery pH values (r = 0.26, p = 0.05). Receiver-operator characteristic curve calculations were all nonsignificant when SpO2 from the last 30 minutes of monitoring was used as a diagnostic test for predicting acidosis at birth. CONCLUSIONS: Intrapartum fetal SpO2 as monitored in the current study was of limited use as a diagnostic test for predicting acidosis at birth, regardless of the SpO2 cutoff value used.

Acidosis↗

PubMed1997

Screening for fetal anomalies by ultrasound at 14 and 21 weeks.

A prospective study of screening for fetal abnormalities and chromosomal defects was carried out by ultrasound examination at 13-15 weeks of gestation and 20-22 weeks; the first scan was performed transvaginally and the second transabdominally. During a 4-year period (1991-95), 3490 unselected consecutive pregnancies with a total of 3514 fetuses were examined. There were 21 chromosomally abnormal fetuses, including ten with trisomy 21, and, in 19 (90.5%), fetal defects were detected at the first and/or second ultrasound examination. The most effective marker for chromosomal defects was increased nuchal translucency thickness (> or = 4 mm) at the 13-15-week scan, which was present in seven of the ten fetuses with trisomy 21 and in six of the 11 with other chromosomal abnormalities.

Adult↗

PubMed1996

[The indications for the management of fetuses with choroid plexus cysts].

Choroid plexus cysts (CPC) in the fetus are still the subject of considerable debate in the literature. Because of their association with aneuploidy, and especially with trisomy 18, of which they are an ultrasonographic marker, the detection of fetal CPC now poses the problem of how these cases should be managed, since most occur in young women (there being no correlation between CPC and age), and since the incidence among the general population is fairly high (around 1%). With the aim of contributing further to the debate, a retrospective study was performed of all cases of fetal CPC diagnosed in our Centre between January 1984 and August 1994, together with a review of the relevant literature. There were 95 cases of fetal CPC with complete neonatal and necroptic data available. These cases included women recruited in the course of routine screening for congenital malformations carried out in our Centre at 14 and 21 weeks gestation, women referred to us from other Centres, and women recruited in the course of amniocentesis indicated for those aged over 35. In all cases in which fetal CPC was detected, a careful ultrasonographic examination was performed to exclude the presence of even the smallest morphologic anomaly. Whenever the fetus was found to have an anomaly karyotyping was done. If the CPC was not associated with any morphologic anomaly, karyotyping was proposed only to those women at risk of aneuploidy because of their age. There were 11 cases of trisomy 18, all of which presented morphologic anomalies associated with CPC. Some of these anomalies where "minor", however, and therefore difficult to assess even when a careful ultrasonographic examination was performed by an experienced operator (Intra ventricular septal defect, single umbilical artery). In 2 cases, CPC was associated with trisomy 21. Both women were aged over 35. All the other cases of CPC not associated with morphologic anomaly were normal on postnatal examination. From a meta-analysis of the literature, two distinct management protocols emerge for the problem of "isolated CPC detected at ultrasonographic examination". One group of authors recommends karyotyping for all women with fetal CPC, considering the presence of CPC in itself a risk factor for aneuploidy. The second group, to which we ourselves belong, believes it is sufficient to perform a careful ultrasonographic examination so as to exclude the presence of other morphologic anomalies associated with the CPC. Karyotyping should be proposed only to women at risk of aneuploidy because of their age (> 35). A review of the biggest series reported in the literature shows that, of a total of 1670 fetuses with CPC, 94 were trisomy 18. None of the cases of CPC "in isolation" emerged as being associated with this aneuploidy. However, numerous cases of trisomy 18 have been described in which CPC is associated with "minor" morphologic anomalies in the fetus which may be difficult to detect. It is therefore essential to perform a careful ultrasonographic examination in all cases of CPC, preferably in a Centre with specialist knowledge of ultrasonography. If this option is not available, then karyotyping of all women with fetal CPC is clearly advisable.

Abnormalities, Multiple↗

PubMed1995

Endometrial assessment by transvaginal sonography and histological findings after D & C in women with postmenopausal bleeding.

A total of 149 women with postmenopausal bleeding underwent transvaginal sonography, hysteroscopy and dilatation and curettage in order to study the diagnostic accuracy of several ultrasound parameters in assessing endometrial pathology and to determine the most sensitive cut-off value of endometrial thickness for the exclusion of endometrial lesions. In distinguishing pathological from normal endometrium, transvaginal sonography showed a sensitivity of 69.3%, specificity of 82.7%, positive predictive value of 74.1% and negative predictive value of 72.1%. In detecting premalignant and malignant endometrial pathology, transvaginal sonography showed a sensitivity, specificity, positive predictive value and negative predictive value of 55%, 96.1%, 68.7% and 93.2%, respectively. Considering endometrial thickness as a single parameter, the most sensitive cut-off for defining normality was 4 mm; nevertheless, in the group of patients that had an endometrial thickness less than 4 mm, there was one case of malignancy (sensitivity, 95.2%; specificity, 49.4%; positive predictive value, 57.3%; and negative predictive value, 93.5%). Transvaginal sonography combined evaluation (morphology, thickness and color Doppler) showed a poor diagnostic accuracy in detecting endometrial pathology and in differentiating between endometrial benign lesions, endometrial polyps and adenocarcinoma in women with postmenopausal bleeding. Endometrial thickness evaluated with transvaginal sonography was preferable but not sensitive enough to exclude endometrial pathology.

Adult↗

PubMed1995

Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer. Carboplatin was given at a fixed target area under the concentration-time curve of 6.0 by the Calvert formula, whereas paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175, 200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study since the highest level achieved (250 mg/m2) required modification because of nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks.

Adult↗

PubMed1994

Management of premature rupture of membranes at term: randomized trial.

OBJECTIVE: We hypothesize that expectant management in the presence of premature rupture of membranes at term would result in a lower cesarean birth rate with no increase in maternal, fetal, or neonatal infection. STUDY DESIGN: Term patients who consented to the study were randomly allocated either to expectant management for 48 hours or to induction of labor 8 hours after premature rupture of membranes. Premature rupture of membranes was confirmed by sterile speculum examination of the vagina. Patients randomized to expectant management were transferred to antenatal care and were not examined vaginally until they went into labor. Patients randomized to induction of labor had induction with oxytocin 8 hours after premature rupture of membranes. RESULTS: Two hundred sixty-two patients were randomized to the expectant management and induction of labor groups. The cesarean birth rate and the clinical diagnosis of postpartum endometritis was not significantly different in the two groups. Pathologic diagnosis of chorioamnionitis and funisitis, however, was significantly greater in the expectant management group (p < 0.05). Eight of the 15 babies with funisitis were admitted to the neonatal intensive care unit for therapy (two in the induction of labor group and six in the expectant management group, p < 0.05). CONCLUSION: Expectant management did not reduce the incidence of cesarean birth and increased the pathologic diagnosis of funisitis and newborn requirements for neonatal intensive care.

Cesarean Section↗

PubMed1994

Lorazepam-enhancement of the antiemetic efficacy of dexamethasone and promethazine. A placebo-controlled study.

This investigation was designed with the objective of improving on currently available antiemetic regimens to counteract the disabling side effects of cancer chemotherapy. The combination of lorazepam, dexamethasone, and promethazine was compared with dexamethasone and promethazine without lorazepam in a double-blind crossover study. The initial study population consisted of 92 women (most with breast cancer) and 7 men; all received moderately or highly emetogenic chemotherapy. Complete data for both periods of therapy were available for 73 of these patients. Crossover analysis showed a highly significant effect of lorazepam in reducing the severity of nausea (p = .003); the severity of vomiting was also reduced, but less dramatically (p = .051). The frequency of all degrees of nausea and vomiting was less with lorazepam, but the difference was not statistically significant. It is concluded that lorazepam added to dexamethasone and promethazine provides an effective regimen for counteracting the emetic side effects of cancer chemotherapy.

Adult↗

PubMed1993

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer.

A total of 53 patients with advanced lung cancer [non-small-cell (NSC), 21; small-cell (SC), 32] were treated with brequinar sodium. All of the NSC patients were chemotherapy-naive, but 31/32 (97%) SC patients had failed a multiagent chemotherapy program prior to study entry. Brequinar was given intravenously at a median weekly dose of 1200 mg/m2. The toxicity was moderate, with 19 patients (36%) experiencing grade 3 or 4 toxicity. Objective responses were observed in one NSC and two SC patients. We conclude that at this dose and on this schedule, brequinar does not have sufficient activity in patients with NSC or in patients with previously treated SC to warrant further evaluation. However, since responses were observed in previously treated SC lung-cancer patients, further evaluation in chemotherapy-naive patients may be warranted.

Aged↗